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hematology/oncology
Neutropenia in Pediatric
Practice
George B. Segel, MD,* Jill
S. Halterman, MD, MPH
Author Disclosure
Drs Segel and
Halterman did not
Objectives
1. Describe when a patient has true neutropenia, understanding the variation with age
and ethnic background.
2. Know the relative risk of infection at various values of the absolute neutrophil count.
3. Discuss the differences between inherited and acquired causes of neutropenia.
4. List the initial studies to evaluate patients who have neutropenia.
Introduction
The significance of neutropenia is a common query to hematology specialists from primary
care physicians. Severe neutropenia is defined as an absolute neutrophil count (ANC) of
fewer than 500/mcL (0.5109/L) and is a common and expected complication of
chemotherapy for childhood neoplasms. This article considers those patients who have
neutropenia unrelated to chemotherapy toxicity. This type of neutropenia may be noted
when a complete blood count (CBC) is performed in a sick newborn, a febrile child, a child
taking chronic medication, or as part of a routine evaluation. Severe hereditary conditions
such as Kostmann syndrome and certain immunodeficiency syndromes associated with
neutropenia are rare, perhaps 1 per 100,000, and are more likely to present in neonates and
infants, although acquired conditions such as immune neutropenia and neutropenia
related to infection also occur in this age group. A mild-to-moderate decrease in the ANC
(percent neutrophils times the total white count) frequently is seen in viral illness or related
to medication use as well as in some healthy persons of African ancestry. A number of
inherited conditions associated with neutropenia are associated with other congenital
anomalies such as dysplastic thumbs in Fanconi anemia, albinism in Chediak-Higashi
syndrome, and dwarfism in the cartilage hair or Shwachman-Diamond syndromes.
Associate Professor of Pediatrics, Division of General Pediatrics, University of Rochester School of Medicine & Dentistry,
Rochester, NY.
12 Pediatrics in Review Vol.29 No.1 January 2008
hematology/oncology
Table 1.
neutropenia
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Age
Mean
(Range)
Mean
(Range)
Mean
(Range)
Mean
Mean
Birth
12 h
24 h
1 wk
2 wk
1 mo
6 mo
1y
2y
4y
6y
8y
10 y
16 y
21 y
18.1
22.8
18.9
12.2
11.4
10.8
11.9
11.4
10.6
9.1
8.5
8.3
8.1
7.8
7.4
(9.0 to 30.0)
(13.0 to 38.0)
(9.4 to 34.0)
(5.0 to 21.0)
(5.0 to 20.0)
(5.0 to 19.5)
(6.0 to 17.5)
(6.0 to 17.5)
(6.0 to 17.0)
(5.5 to 15.5)
(5.0 to 14.5)
(4.5 to 13.5)
(4.5 to 13.5)
(4.5 to 13.0)
(4.5 to 11.0)
11.0
15.5
11.5
5.5
4.5
3.8
3.8
3.5
3.5
3.8
4.3
4.4
4.4
4.4
4.4
(6.0 to 26.0)
(6.0 to 28.0)
(5.0 to 21.0)
(1.5 to 10.0)
(1.0 to 9.5)
(1.0 to 9.0)
(1.0 to 8.5)
(1.5 to 8.5)
(1.5 to 8.5)
(1.5 to 8.5)
(1.5 to 8.0)
(1.5 to 8.0)
(1.8 to 8.0)
(1.8 to 8.0)
(1.8 to 7.7)
61
68
61
45
40
35
32
31
33
42
51
53
54
57
59
5.5
5.5
5.8
5.0
5.5
6.0
7.3
7.0
6.3
4.5
3.5
3.3
3.1
2.8
2.5
(2.0 to 11.0)
(2.0 to 11.0)
(2.0 to 11.5)
(2.0 to 17.0)
(2.0 to 17.0)
(2.5 to 16.5)
(4.0 to 13.5)
(4.0 to 10.5)
(3.0 to 9.5)
(2.0 to 8.0)
(1.5 to 7.0)
(1.5 to 6.8)
(1.5 to 6.5)
(1.2 to 5.2)
(1.0 to 4.8)
31
24
31
41
48
56
61
61
59
50
42
39
38
35
34
1.1
1.2
1.1
1.1
1.0
0.7
0.6
0.6
0.5
0.5
0.4
0.4
0.4
0.4
0.3
6
5
6
9
9
7
5
5
5
5
5
4
4
5
4
0.4
0.5
0.5
0.5
0.4
0.3
0.3
0.3
0.3
0.3
0.2
0.2
0.2
0.2
0.2
2
2
2
4
3
3
3
3
3
3
3
2
2
3
3
*Numbers of leukocytes are in thousands/mcL (109/L), ranges are estimates of 95% confidence limits, and percentages refer to differential counts.
Neutrophils include band cells at all ages and a small number of metamyelocytes and myelocytes in the first few postnatal days.
From Dallman PR. Blood and blood-forming tissues. In: Rudolph AM, ed. Rudolphs Pediatrics. 16th ed. New York, NY: Appleton-Century-Crofts;
1977:1178, with permission.
Risk Assessment
For patients older than 1 year of age, mild neutropenia is
defined as an ANC of 1,000 to 1,500/mcL (1.0 to
1.5109/L), moderate neutropenia as an ANC of
500 to 1,000/mcL (0.5 to 1.0109/L), and severe
neutropenia as an ANC of less than 500/mcL
(0.5109/L). Usually, patients are highly susceptible to
bacterial infection if the ANC is less than 500/mcL
(0.5109/L), with the risk of infection greatest at the
lowest ANCs. Increased infection risk also is related to
longer durations of neutropenia and is highest if the
neutrophil count remains low without recovery. If neutrophils can be mobilized to respond, infection is less
likely to occur, as can be seen in immune neutropenia, a
condition in which there is myeloid hyperplasia and
heightened neutrophil production. Although serious
bacterial infections are observed when the ANC is between 500 and 1,000/mcL (0.5 and 1.0109/L), they
are much less frequent or severe. There is little or no
heightened infectious risk if the ANC is greater than
1,000/mcL (1.0109/L).
hematology/oncology
neutropenia
Table 2.
History
Physical Examination
Blood smear
Coombs test (direct antiglobulin test) for associated
hemolytic anemia
Immunoglobulins (IgA, IgG, IgM)
Serology (Epstein-Barr virus, cytomegalovirus,
respiratory syncytial virus, parvovirus, etc, as
indicated clinically)
Antineutrophil antibodies
Acquired Neutropenia
Infection
When evaluating the child who has neutropenia, the
acquired neutropenias are considered first because of
their greater frequency (Table 4). The most common
underlying cause for mild-to-moderate neutropenia is
transient marrow suppression due to a variety of viral
infections. Neutropenia is seen in patients who have
Epstein-Barr virus, respiratory syncytial virus, influenza A
and B, hepatitis, and human herpesvirus 6 infections
as well as the exanthems (to which most children are
immunized), including varicella, rubella, and rubeola.
Neutropenia occurs often during the first few days of the
viral illness and persists for 3 to 8 days. Severe bacterial
infection also may cause neutropenia rather than neutrophilia, which can be transient if the bacterial infection is
treated effectively. Other bacterial or rickettsial diseases
such as typhoid fever, tuberculosis, and Rocky Mountain
spotted fever may cause neutropenia.
Drug-induced
A variety of medications (Table 5), including antibiotics,
anticonvulsants, and anti-inflammatory agents, have
been associated with neutropenia, a frequent reason for
referral to hematology. The dilemma is how to treat the
patient who requires the particular medication that is
causing a potentially dangerous adverse effect. If the
drug-induced neutropenia is idiosyncratic, its severity
and persistence may be impossible to predict, and it is
difficult to avoid discontinuing the drug. A similar situ-
hematology/oncology
Table 3.
neutropenia
Test
Findings
ANC less than lower limit for age (Table 1) anemia and thrombocytopenia
Increased if RBC destruction, as in Evans syndrome (or bleeding)
Decreased in marrow failure syndromes
Confirms decreased ANC
Morphologic abnormalities of neutrophils, as in Chediak-Higashi syndrome
Associated RBC or platelet findings
Detects antibodies to RBC, as in Evans syndrome or systemic lupus
erythematosus
Screen for systemic lupus erythematosus
May be found in alloimmune or autoimmune neutropenia
Screen for underlying immunodeficiency
IgG and IgA may be decreased and IgM elevated
Decreased T, B, or NK cells in underlying immunodeficiency
May show no maturation beyond the promyelocyte stage in severe
congenital neutropenia; myeloid hyperplasia with few or no bands or
mature neutrophils in immune neutropenia
Cytogenetics may reveal a neoplastic clone, as in leukemia
Specific for genetic diagnosissee Table 6 for specific genes
Blood Smear
Coombs Test (Direct Antiglobulin Test)
ANA Anti-double-stranded DNA
Antineutrophil Antibody
IgG, IgA, IgM
Lymphocyte Subtypes
Marrow Examination
Low serum trypsinogen and elevated stool fat found in ShwachmanDiamond syndrome
Serum vitamin B12, RBC, and serum folic acid
ANAantinuclear antibody, ANCabsolute neutrophil count, CBCcomplete blood count, RBCred blood cell.
Immune
Neonatal alloimmune neutropenia results from the transfer of fetal cells to the maternal circulation, causing the
mother to produce antibody to fetal antigens not present
on her own cells in a manner similar to Rh disease.
A variety of neutrophil-specific antigens have been identified and are designated HNA-1a (NA1), HNA-1b
(NA2), HNA-2a (NB1), HNA-3a (5b), HNA-4a
(MART), and HNA-5a (OND). Because the half-life of
IgG is approximately 5 to 6 weeks, alloimmune neutropenia usually disappears after age 2 to 3 months. If
infections are associated with the neutropenia, granulocyte colony-stimulating factor (G-CSF) may be used to
stimulate a heightened neutrophil count.
Passive transfer of maternal antibody also may cause
neonatal neutropenia. Pregnant women who have either
primary immune neutropenia or immune neutropenia
due to a disease such as lupus may transfer IgG antineu-
hematology/oncology
Table 4.
neutropenia
Acquired Neutropenia
Condition
Pathogenesis
Occurrence
Associated Findings
Infection
Common
Less common
Severe infection
Common
Less common
Common
Underlying condition
Drug-induced
Autoimmune
Newborn Immune
Chronic Idiopathic
Monocytosis common
Rare
Common
Sequestration
Hypersplenism
Nutritional
Rare in children
Hypersegmented neutrophils
Chronic Idiopathic
Chronic idiopathic neutropenia likely represents a variety
of disorders and is not well characterized. Some of the
patients classified as having chronic idiopathic neutropenia actually may have immune neutropenia or familial
benign neutropenia. The idiopathic diagnosis may be
considered when other known causes have been eliminated. The clinical severity appears to be related to the
16 Pediatrics in Review Vol.29 No.1 January 2008
Sequestration
Splenomegaly and hypersplenism from any cause may
result in mild neutropenia (1,000 to 1,500/mcL [1.0 to
1.5109/L]) due to sequestration. Enlarged spleens
may be present in patients who have chronic hemolytic
anemias, liver disease, or portal hypertension and in
metabolic disorders such as Gaucher disease. These conditions also may result in anemia and thrombocytopenia.
Results of the marrow examination are normal or show
mild hyperplasia of all elements. Usually, this problem
does not require treatment unless the cytopenias are
profound or management of the underlying condition
requires treatment. In some cases, splenectomy is necessary.
hematology/oncology
Table 5.
neutropenia
Drug
Analgesics/Anti-inflammatory Agents
Aminopyrine
Ibuprofen
Indomethacin
Phenylbutazone
Antibiotics
Chloramphenicol
Penicillins
Sulfonamides
Anticonvulsants
Phenytoin
Carbamazepine
Antithyroid Agents
Propylthiouracil
Cardiovascular Agents
Hydralazine
Procainamide
Quinidine
Hypoglycemic Agents
Chlorpropamide
Tranquilizers
Chlorpromazine
Phenothiazines
Other
Cimetidine, ranitidine
Levamisole
Direct
Suppression
Metabolite
Suppression
Immune
Destruction
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Reproduced from Dinauer MC. The phagocyte system and disorders of granulopoiesis and granulocyte function. In: Nathan DG, Orkin SH, Look AT,
Ginsburg D, eds Nathan and Oskis Hematology of Infancy and Childhood. 6th ed. Philadelphia, Pa: WB Saunders Company; 2003:9231010 with permission.
Nutritional Deficiency
Both vitamin B12 and folic acid deficiency may result in
ineffective hematopoiesis with megaloblastic erythropoiesis. Patients who develop megaloblastic anemia generally are adults. In addition to megaloblastic anemia, the
impairment in DNA processing may result in neutropenia. Neutrophil nuclear maturation is impaired, leading
to hypersegmentation of the neutrophil nuclei in the
blood as well as ineffective marrow proliferation and
maturation. Treatment involves replacement of the deficient factor.
autosomal recessive condition (Kostmann syndrome) involving mutations in the HAX1 gene that is involved in
signal transduction. It also may be inherited as an autosomal dominant condition, with mutations in the neutrophil elastase gene (ELA2) or, more rarely, in the GFI1
gene that targets ELA2. It has been suggested that such
gene mutations result in accelerated apoptosis of myeloid
precursors. Examination of the marrow reveals an arrest
at the promyelocyte stage of development (a picture of
bone marrow in severe congenital neutropenia is available in the online edition of this issue of Pediatrics in
Review [www.pedsinreview.org]). Few or no myelocytes, metamyelocytes, bands, or mature neutrophils are
seen, and there may be an associated monocytosis and
eosinophilia in the blood. Affected patients have a very
high risk of developing a myelodysplastic syndrome or
acute myelogenous leukemia, a consequence that has
become more evident as patients live longer with treatment using G-CSF. Table 7 describes G-CSF administration.
Pediatrics in Review Vol.29 No.1 January 2008 17
hematology/oncology
Table 6.
neutropenia
Inherited Neutropenia
Condition
Inheritance
Pathogenesis
Severe Congenital
(Kostmann)
AR
Severe Congenital
AD and
sporadic
Cyclic
AD
Shwachman-Diamond
Syndrome
AR
Familial Benign
AD
Blackfan Diamond
Syndrome
Dysgammaglobulinemia or
Hyper-IgM
Occurrence
Usually XR
DKC1 (TERC or TERT in
(also AR and AD) mutations
AD)
Telomerase defect,
ribosomal dysfunction
Sporadic 75% RPS19 mutations that
AR and AD
affect a ribosomal
protein in 25% of
families
? Mechanism of
erythropoietic failure
Many patients respond
to glucocorticoids
XR (also AR) CD40 ligand mutations
? Immune neutropenia,
but antineutrophil
antibody is negative
AD (also ?AR) Imbalance in pro- and Case reports
anti-apoptosis
Defect in CXCR4
receptor leading to
failure of neutrophils
to leave the marrow
Associated Findings
Dysplastic thumbs,
pancytopenia, other
anomalies
Abnormal skin pigmentation,
leukoplakia, dystrophic nails
Erythroid failure syndrome
Neutropenia in 25% to 40%
Thumb and craniofacial
anomalies
Increased RBC adenosine
deaminase
Leukemia risk of 2% to 3%
2IgG, 2IgA, 1IgM
May have immune
thrombocytopenia and
anemia
Neutropenia only seen in XR
Warts, hypogammaglobulinemia,
infections, and myelokathexis
(WHIM)
hematology/oncology
Table 6.
neutropenia
Condition
Inheritance
Chediak-Higashi Syndrome AR
Reticular Dysgenesis
AR
Cartilage Hair
AR
Metabolic Glycogen
AR
Storage Disease 1b
(also aminoacidopathies)
Griscelli Syndrome Type 2
AR
Barth Syndrome
XR
Wiscott-Aldrich Syndrome XR
Unknown or
multifactorial
Pathogenesis
Occurrence
Rare
CHS1 ?defect in
lysosomal fission
Abnormal protein
trafficking
Decreased neutrophil
chemotaxis,
degranulation,
and killing
Stem cell failure in
Rare
lymphoid and
myeloid development
RMRP mutations
Rare
Defect in a ribonuclear
protein ribonuclease
G6PT1 mutations
(glucose-6phosphate
translocase) in 1b
RAB27A mutations
Impaired lytic granule
release
Rare
Associated Findings
2NK and T-cell function
Albinism
Neurologic damage and giant
lysosomes
Severe combined
immunodeficiency with
neutropenia
Fine hair, short-limbed,
dwarfism, lymphopenia,
2CD4 and 2CD8 cells
Infections, particularly varicella
zoster
Hypoglycemia, dyslipidemia,
1uric acid, 1lactic acid, and
neutropenia in most patients
Partial albinism, neutropenia,
infections, and
thrombocytopenia with
hemophagocytosis and T-cell
defect
Dilated cardiomyopathy
Skeletal myopathy
Mitochondrial abnormalities
Impaired lymphoid development
and maturation of monocytes
Associated with eczema,
thrombocytopenia, and
immune deficiency
Infections of the upper and
lower respiratory tracts in
one third of patients
ARautosomal recessive, ADautosomal dominant, ANCabsolute neutrophil count, Igimmunoglobulin, NKnatural killer, RBCred blood cell,
XRX-linked recessive.
Cyclic
Cyclic neutropenia is characterized by approximately
21-day cycles of changing neutrophil counts, with neutropenia spanning 3 to 6 days. The nadir of the neutrophil count may be in the severe range. Fever and oral
ulcerations usually are seen during the nadir. Patients
also may develop gingivitis, pharyngitis, and skin infections. However, by the time the patient comes to medical
attention, the neutrophil count may be recovering.
Therefore, diagnosing cyclic neutropenia may require
obtaining blood counts two to three times per week for
4 to 6 weeks in an effort to observe the periodicity of the
cycle.
More serious infections include pneumonia, necrotizing enterocolitis with peritonitis, and Escherichia coli or
Clostridium sepsis. Marrow findings reflect the state of
neutropenia. Prior to the ANC nadir, the marrow may
resemble that associated with severe congenital neutropenia before proceeding to a recovery phase. The periodicity of marrow activity also may be seen in the erythroid series. As in severe congenital neutropenia,
mutations occur in the ELA2 gene, but at different
locations (Table 6). Also, there does not appear to be an
increased risk of myelodysplasia or acute myelogenous
leukemia. Prophylactic G-CSF has been recommended
to prevent severe symptoms at the nadir of the cycle.
Pediatrics in Review Vol.29 No.1 January 2008 19
hematology/oncology
Table 7.
neutropenia
Treatment of Neutropenia
Granulocyte Colony-stimulating
Factor
Glucocorticoids
Nutritional
Splenectomy
Medication Revision
Antibiotics
Granulocyte Transfusion
Shwachman-Diamond Syndrome
Patients who have Shwachman-Diamond syndrome usually have a mild-to-moderate degree of neutropenia in
association with exocrine pancreatic insufficiency, short
stature, metaphyseal dysplasia, marrow failure, and the
risk of myelodysplasia and acute myelogenous leukemia.
A defect in RNA processing leads to a failure of neutrophil development. Malabsorption and failure to thrive
are common problems, and affected patients may develop infections because of the neutropenia and a possible defect in chemotaxis. G-CSF has been used when the
neutropenia is symptomatic; pancreatic replacement
therapy is required.
hematology/oncology
Table 8.
neutropenia
ANC
1,000 to 1,500/mcL
(1.0 to 1.5109/L)
Mild
500 to 1,000/mcL
(0.5 to 1.0109/L)
Moderate
<500/mcL
(0.5109/L)
Severe
Etiology of Fever
Management
Outpatient/Hospital
Viral (frequent)
Supportive
Outpatient
Bacterial: URI
(sinusitis, purulent
rhinitis), otitis
media, local skin
infections
Indicated PO antibiotics
Outpatient
Bacterial pneumonia,
systemic
symptoms, GU
infections,
lymphadenitis
Blood cultures
Specific cultures
Best estimate
antibiotics
Observation for
progression
Supportive
Outpatient unless
progression
Bacterial: URI
(sinusitis, purulent
rhinitis), otitis
media, local skin
infections
Outpatient/Hospital*
Bacterial pneumonia,
systemic
symptoms, GU
infections,
lymphadenitis
Assume bacterial
Blood cultures
Specific cultures
Sepsis evaluation
Parenteral broadspectrum antibiotics
Blood cultures
Specific cultures
Sepsis evaluation
Parenteral broadspectrum antibiotics
Hospital
Viral
Outpatient
Hospital
ANCabsolute neutrophil count, GUgenitourinary, IVintravenous, POoral, URIupper respiratory tract infection.
*Either outpatient or hospital care may be appropriate for children who have moderate neutropenia and local infection, depending on the patients underlying
disorder and the anticipated time for recovery of the ANC. Children who have congenital/chronic neutropenia likely would benefit from treatment in the
hospital because recovery of the ANC is less likely without cytokine treatment. In contrast, neutropenia due to viral suppression, antibody effect, or some
medication exposures may allow a better response to localized bacterial infection and be managed on an outpatient basis.
been formulated for patients who have chemotherapyinduced neutropenia, relatively few data are available for
patients who have neutropenia not associated with cancer treatment. Fever is defined as a temperature greater
than 101F (38.3C) or a temperature of at least 100.4F
(38C) for longer than 1 hour. Most authors categorize
the severity of neutropenia into three groups (Table 8).
The decision surrounding treatment and potential hospitalization depends on the likelihood of bacterial infection, the location and severity of the infection, the severity of the neutropenia, and the likelihood and timeframe
of neutrophil recovery. Furthermore, the age of the
patient, the proximity of specialized medical care, and
the reliability of the guardians should be considered in
the management decision. Table 8 presents a starting
point for consideration of what to do and is based on
the principles used in the care of neutropenic chemother-
hematology/oncology
neutropenia
Bacterial Causes of
Febrile Episodes in
Neutropenic Patients
Table 9.
hematology/oncology
Summary
Neutropenia unrelated to chemotherapy toxicity occurs
in a number of clinical settings. The most common
conditions associated with neutropenia are those that are
acquired, including viral infection, neutropenia associated with various medications, and immune neutropenia.
Inherited neutropenias are rarer and often more pro-
neutropenia
Suggested Reading
Atallah E, Schiffer CA. Granulocyte transfusion. Curr Opin Hematol. 2006;13:45 49
Baehner RL. Drug-induced neutropenia and agranulocytosis. UpToDate. 2007. Available at: www.uptodate.com
Bertuch AA, Strother D. Fever in children with non-chemotherapyinduced neutropenia. UpToDate. 2007. Available at: www.uptodate.com
Bertuch AA, Strother D. Management of fever in children with
non-chemotherapy-induced neutropenia. UpToDate. 2007.
Available at: www.uptodate.com
Beutler E, West C. Hematologic differences between AfricanAmerican and whites: the roles of iron deficiency and alphathalassemia on hemoglobin levels and mean corpuscular volume. Blood. 2005;106:740 745
Boxer LA. Neutrophil abnormalities. Pediatr Rev. 2003;24:52 62
Boxer LA, Stein S, Buckley D, Bolyard AA, Dale DC. Strong
evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations. J Pediatr.
2006;148:633 636
Hughes WT, Armstrong D, Bodey GP, et al. 1997 guidelines for
the use of antimicrobial agents in neutropenia patients with
unexplained fever. Clin Infect Dis. 1997;25:551573
Klein C, Grudzien M, Appaswamy G, et al. HAX1 deficiency causes
autosomal recessive severe congenital neutropenia (Kostmann
disease). Nat Genet. 2007;39:86 92
Lehrnbecher T, Welte K. Haematopoietic growth factors in children with neutropenia. Br J Haematol. 2002;116:28 56
Palmblad JEW, von dem Borne AEG Jr. Idiopathic, immune,
infectious and idiosyncratic neutropenias. Semin Hematol.
2002;39:113120
Skokowa J, Germeshausen M, Zeidler C, Welte K. Severe congenital neutropenia: inheritance and pathophysiology. Curr Opin
Hematol. 2007;14:2228
hematology/oncology
neutropenia
PIR Quiz
Quiz also available online at www.pedsinreview.org.
6. A 6-year-old boy presents with a history of a temperature to 103F (39.4C) and ulcerations on his lips
and buccal mucosa 2 days ago. The child has some small, slightly ulcerated areas on his lips and is
afebrile. His mother reports two similar episodes in the past 2 months. He has a white blood cell count of
2.9103/mcL (2.9109/L), hemoglobin of 11.4 g/dL (114 g/L), and platelet count of 349103/mcL
(349109/L). His differential count is 40% neutrophils, 49% lymphocytes, 9% monocytes, and 2%
eosinophils. Of the following, the best laboratory test to evaluate this child is:
A.
B.
C.
D.
E.
Antineutrophil antibodies.
Blood counts two to three times a week for 4 to 6 weeks.
Bone marrow aspiration.
Herpes cultures.
Repeat of the count in 1 week to see if it normalizes.
7. A previously well 3-year-old boy presents with 4 days of temperature up to 104F (40C). He is in no
acute distress and does not appear ill. The only abnormal physical finding is mild rhinitis. A complete
blood count reveals a white blood cell count of 1.5103/mcL (1.5109/L), hemoglobin of 12.8 g/dL
(128 g/L), and platelet count of 349103/mcL (349109/L). His differential count is 2% neutrophils,
80% lymphocytes, 10% monocytes, and 6% eosinophils. A blood culture is obtained. After a single dose
of acetaminophen, the child becomes afebrile. Of the following, the most appropriate next step is to:
A.
B.
C.
D.
E.
Give a dose of broad-spectrum antibiotics and admit the child for continuing intravenous antibiotics.
Give a dose of ceftriaxone and see the child the following morning.
Observe the child in the emergency department overnight.
See the child the following morning but tell the parents to call sooner if he becomes more ill.
Start amoxicillin and clavulanic acid orally and see the child the following morning.
8. The mother of a well 4-month-old child would like you to obtain a complete blood count to make sure
her baby is OK. You determine that she has no specific anxieties or reasons for suspecting a problem. Of
the following, the most appropriate response is to:
A. Explain that a routine complete blood count is obtained at 9 months of age.
B. Explain that only a hemoglobin or hematocrit is measured routinely in well children at 9 to 12 months
of age.
C. Explain that there is no reason to obtain any blood counts for well children at any time.
D. Order a complete blood count.
E. Order a complete blood count with a differential white blood cell count.
9. What is the most common underlying cause for mild-to-moderate neutropenia?
A.
B.
C.
D.
E.
2
2
5
2
6
to
to
to
to
to
3
3
6
3
7
days.
weeks.
weeks.
months.
months.
Index of Suspicion
Cherilyn Hall, Allen Friedland, Sumathi Sundar, Kathryn S. Torok, Mananda S.
Bhende, Grace Pecson and Carolyn Leedy
Pediatr. Rev. 2008;29;25-30
DOI: 10.1542/pir.29-1-25
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/cgi/content/full/29/1/25
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
index of suspicion
Case 1 Presentation
Author Disclosure
Drs Hall, Friedland, Sundar, Torok,
Bhende, Pecson, and Leedy did not
disclose any financial relationships
relevant to these cases.
Case 2 Presentation
A 14-year-old girl is seen in the ED
because of 2 days of lower abdominal
and back pain. The pain is a constant,
dull, bandlike ache of 9/10 in intensity. She denies fever, nausea, vomiting, diarrhea, melena, hematochezia,
dysuria, hematuria, vaginal discharge, or constitutional symptoms.
She is premenarchal and denies sexual activity.
She had an appendectomy at age 5
years complicated by the development of necrotic bowel, requiring a
small bowel resection. After recovering from surgery, she developed
chronic intermittent abdominal pain,
ultimately diagnosed as being functional. She describes her current pain
as different from her chronic abdominal pain.
On physical examination, the girl
is uncomfortable but in no apparent
distress and looks healthy. All vital
signs are normal. Her breast development is at Sexual Maturity Rating 5.
She is thin and easy to examine. Her
back is straight, with no tenderness
to palpation over the spine, paraspinal muscles, or costovertebral angles.
Her abdominal examination reveals a
10-cm linear, well-healed vertical
scar down the midline and a slightly
protuberant lower abdomen. Palpation reveals a large, well-defined, firm
mass extending from the pelvis halfway to the umbilicus in the mid-line.
Mild pain is elicited on deep palpation of the left lower quadrant, with
no guarding or rebound tenderness.
Additional examination reveals the
diagnosis.
Case 3 Presentation
A 6-month-old boy is readmitted because of respiratory distress and hypPediatrics in Review Vol.29 No.1 January 2008 25
index of suspicion
Case 1 Discussion
At laparotomy, intestinal malrotation
with small bowel obstruction at the
level of the distal ileum was found.
26 Pediatrics in Review Vol.29 No.1 January 2008
The Condition
Intestinal malrotation is an anatomic
anomaly caused by arrest of normal
rotation and mesenteric fixation of
the embryonic gut, a failure of normal embryologic gut formation that
occurs between the 5th and 10th
weeks of gestation. The result of a
nonrotated gut is location of the colon on the left side and a narrowbased mesentery in the upper midabdomen that is fixed to the right
abdominal wall by adhesions known
as Ladd bands. Anomalies commonly
associated with intestinal malrotation
include duodenal atresia (50%) and
jejunal atresia (33%). Disorders of intestinal rotation and mesenteric fixation to the posterior abdominal cavity are also common in infants and
children who have congenital diaphragmatic hernia, gastroschisis, and
omphalocele.
Intestinal malrotation is believed
to occur in 1 per 200 to 1 per 500 live
births, with symptomatic malrotation occurring in 1 per 6,000 live
births. Symptomatic malrotation is
evident clinically in the first postnatal
month in 64% of patients, and 82%
are diagnosed in the first postnatal
year; 18% to 25% of symptomatic patients are diagnosed at 1 year of age
and older. Because malrotation is discovered incidentally in some patients, the true number of patients
who have malrotation that is never
detected can only be estimated.
Malrotation can cause duodenal
obstruction because of impingement
on the bowel by the Ladd bands. The
most serious consequence is a midgut volvulus, a life-threatening condition in which the intestine twists on
the mesenteric stalk and compromises its blood supply, which can
lead rapidly to infarction of the entire
small bowel. Both duodenal obstruction from Ladd bands and volvulus
may occur intermittently, characterized by chronic and sometimes vague
Differential Diagnosis
The differential diagnosis for intestinal malrotation varies according to
the age of presentation. In infancy
and childhood, conditions to consider include necrotizing enterocolitis, pyloric stenosis, intussusception,
ileus due to sepsis or meconium,
Hirschsprung disease, appendicitis,
and duodenal atresia. In older children and adults, similar symptoms
can result from inflammatory bowel
syndrome, pancreatitis, or acute abdominal conditions such as appendicitis.
Diagnosis
Diagnostic evaluation generally requires a degree of suspicion for volvulus and, in a stable patient, can
index of suspicion
Therapy
Intestinal malrotation requires surgical intervention. The Ladd procedure is recommended for intestinal
malrotation regardless of age or
symptoms. This operation includes
lysis of adhesions, widening of the
mesenteric base, and positioning of
the bowel in a place of nonrotation as
well as appendectomy and resection
of any necrotic bowel. The urgency
of the operation is dictated by the
presence of intestinal ischemia
caused by volvulus. In the setting of
malrotation without volvulus, most
surgeons advocate the Ladd procedure as a prophylactic maneuver to
reduce the probability of volvulus.
This patient underwent a Ladd
Case 2 Discussion
Examination of the patients genitalia revealed a normal vulva and labia
with Sexual Maturity Rating 5 distribution of pubic hair. A bulging, bluish membrane that was firm to palpation protruded from the introitus
(Figure). Abdominal and pelvic ultrasonography performed to confirm
the diagnosis of imperforate hymen
revealed a grossly dilated vagina filled
with homogeneous, echogenic material consistent with hematocolpos.
No other urogenital abnormalities
were present. The patient was admitted for a hymenectomy and evacuation of retained clotted blood. After
an uncomplicated hymenectomy, the
The Condition
Imperforate hymen is the most common obstructive genital tract anomaly occurring in females, having an
incidence of 1 in 1,000 to 1 in
10,000 individuals. Most commonly,
imperforate hymen is detected during adolescence either during an
evaluation for asymptomatic primary
amenorrhea or an investigation of
abdominal, back, or pelvic pain in the
premenarchal female. Other complaints include urinary retention and
pain with defecation. The pain is due
to the collection of menstrual blood
in the vagina and uterus. An imperforate hymen also can be detected on
prenatal ultrasonography as hydrocolpos if it is associated with urinary
obstruction and a urogenital fistula,
during a newborn examination as a
mucocolpos from maternal estrogeninduced secretions, or during a
health supervision visit as a membrane that bulges when the child performs a Valsalva maneuver. The term
hydrometrocolpos is used when both
vagina and uterus are dilated with
fluid.
Imperforate hymen is a sporadic
congenital outflow obstruction
anomaly resulting from the failure of
canalization of the tissue joining the
mullerian ducts and the urogenital
sinus during development. Embryologically, the female genital tract involves the medial migration and midline (horizontal) fusion of the paired
mullerian (paramesonephric) ducts
to form the uterus, cervix, and upper
vagina and the vertical fusion of the
developing ductal system with the
invaginating urogenital sinus to form
the lower vagina and introitus. Horizontal fusion defects result in vaginal
agenesis (also known as mullerian
agenesis
or
Mayer-RokitanskyKuster-Hauser syndrome) and may
Pediatrics in Review Vol.29 No.1 January 2008 27
index of suspicion
Differential Diagnosis
Although an imperforate hymen
should be obvious on physical examination, several conditions may
present with similar complaints and
findings. A history of primary amenorrhea in the presence of a blind or
absent vagina indicates a variety of
developmental anomalies of the genital outflow tract, including imperforate hymen, low-lying transverse vaginal septum, cervical atresia, vaginal
(mullerian) agenesis, and androgen
insensitivity syndrome (AIH). Of
these conditions, imperforate hymen, transverse septum, and cervical
atresia commonly present at the expected time of menarche in a girl
Treatment
Hymenectomy is the definitive treatment for an imperforate hymen.
Abdominal ultrasonography is rec-
index of suspicion
Case 3 Discussion
The baby continued to require supplemental oxygen and demonstrated
respiratory distress with feedings.
A video swallow study showed no
evidence of aspiration. CT scan of the
chest performed to evaluate pulmonary anatomic abnormalities as a
cause for prolonged hypoxia revealed
a vascular structure to the left of the
aorta consistent with a duplicated superior vena cava or anomalous pulmonary venous connection. An ECG
showed right atrial enlargement and
findings consistent with right ventricular hypertrophy. Echocardiography confirmed the diagnosis of unobstructed supracardiac total anomalous pulmonary venous connection
(TAPVC), with the pulmonary veins
draining into the innominate vein.
A large secundum atrial septal defect
(ASD) with right-to-left shunting
also was present.
The Condition
Lessons for the Clinician
A teenage girl who has lower abdominal pain and back pain may bring to
mind an extensive differential diagnosis, leading to extensive laboratory
and radiologic testing. However, the
history and physical examination remain the most useful tools at the
physicians disposal to make the diagnosis. In this case, the patients ad-
index of suspicion
Prognosis
Most patients who have TAPVC do
not survive beyond the first year
without surgery. Emergent surgery
Reference
1. Reich JD, Miller S, Brogdon B, et al. The
use of pulse oximetry to detect congenital
heart disease. J Pediatr. 2003;142:268 272
Index of Suspicion
Cherilyn Hall, Allen Friedland, Sumathi Sundar, Kathryn S. Torok, Mananda S.
Bhende, Grace Pecson and Carolyn Leedy
Pediatr. Rev. 2008;29;25-30
DOI: 10.1542/pir.29-1-25
Updated Information
& Services
Supplementary Material
Reprints
A Flood of Information
Lawrence F. Nazarian
Pediatr. Rev. 2008;29;3-4
DOI: 10.1542/pir.29-1-3
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/cgi/content/full/29/1/3
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
commentary
Commentary
A Flood of Information
Many elements in our lives can overwhelm us and overload our circuits,
including responsibilities, worries, and
conflicting appointments. Even some
treats we enjoy can get to be too much,
such as tomatoes in the garden at the
peak of the season, photographs waiting to be organized, and exceptional
books crying out to be read. Another
flood that threatens to engulf us is
information. Even if we ignore the obviously misleading or irrelevant rivers of
data flowing toward our minds, there is
enough worthwhile, relevant, desirable
information coming our way to sweep
us over the falls.
Restricting our focus to medical
knowledge, and even further to an understanding of pediatric medicine, we
still find that sector of the information
ocean stretching out to the horizon and
getting bigger every year. There used to
be lectures, seminars, workshops, textbooks, and journals. All of these sources
have multiplied, and we have added
continuing medical education courses,
teleconferences, CDs and DVDs, and
that infinite highway to knowledge
about everything under the sun and
beyond, the Internet. No wonder many
practitioners feel they are lost at sea
and going down for the third time.
Pediatrics in Review (PIR) and the
PREP program exist to throw you a life
preserver and a compass. Our primary
mission is to focus on the essentials of
pediatric medicine and to present current thinking about each aspect of that
body of knowledge to keep readers up
to date. We are fortunate to have
access to the content specifications of
the American Board of Pediatrics,
which has created a database that defines that core. In any given 5-year
period, PIR and the PREP SelfAssessment cover that content, allowing readers to refresh their knowledge
in a constant, renewing fashion. In the
process, steady readers are preparing
themselves for the cognitive testing
involved in maintenance of certification.
We continue to recruit our material
from the best teachers in our profession
and to spend countless hours making
what is written readable and lucid. The
individuals who produce PIR at all levels know what it is like to come home
after a long day and try to learn even
more. With that sensitivity, we attempt
to make our teaching as user-friendly
as we can.
Realizing that there are relevant and
interesting topics outside the core content, we have expanded our horizons,
adding two new sections in the last 2
years. Many parents are using or asking
about therapies outside of conventional
medicine, and we publish a regular
series on complementary and alternative treatments. As strong believers in
the role of pediatricians in the wider
community, we publish another regular
feature on community pediatrics that
highlights innovative and effective programs in that area.
Our electronic edition has allowed
us to broaden the spectrum of pediatric
subjects even further. By publishing one
or two articles each month in the
online-only format, we have created
new space to give our readers insights
into topics such as telemedicine, continuing medical education, and the
electronic medical record. The electronic capability has allowed us to provide recordings of heart murmurs as
well as still and moving pictures. The
commentary
Lawrence F. Nazarian, MD
Editor-in-Chief
A Flood of Information
Lawrence F. Nazarian
Pediatr. Rev. 2008;29;3-4
DOI: 10.1542/pir.29-1-3
Updated Information
& Services
Reprints
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/cgi/content/full/29/1/31
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
Figure. These children are participating in a program to help combat obesity and get children more active in Palo Alo, Calif. The
residents involved were Heather Iezza, MD, and Maria Mosquera, MD.
cacy guide for pediatricians, pediatric residents, and child health professionals, which will be available in
the spring of 2008.
Pediatrics in Review to sponsor this
feature.
Updated Information
& Services
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Inhalants
Michael Crocetti and Janet R. Serwint
Pediatr. Rev. 2008;29;33-34
DOI: 10.1542/pir.29-1-33
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/cgi/content/full/29/1/33
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
in brief
In Brief
Inhalants
Michael Crocetti, MD
Bayview Medical Center
Baltimore, Md.
Author Disclosure
Drs Crocetti and Serwint did not
disclose any financial relationships
relevant to this In Brief.
in brief
Janet R. Serwint, MD
Consulting Editor
Inhalants
Michael Crocetti and Janet R. Serwint
Pediatr. Rev. 2008;29;33-34
DOI: 10.1542/pir.29-1-33
Updated Information
& Services
Reprints
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/cgi/content/full/29/1/5
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2008 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
Article
infectious diseases
Author Disclosure
Dr Gershon has
disclosed that she
occasionally is a
consultant and
lecturer for Merck
Objectives
1. Describe the natural history and pathogenesis of varicella and zoster and how these
diseases are related.
2. Explain to patients and parents the complex role of this virus in causing disease and
how the virus spreads.
3. Describe how best to manage patients who have these infections.
4. Discuss how varicella vaccine works, how effective it is in preventing disease, and why
two doses of vaccine are now recommended.
The Pathogen
Varicella-zoster virus (VZV), a close but distinct relative of the other seven human
herpesviruses, including herpes simplex virus (HSV), causes two diseases. Varicella (chickenpox), a generalized illness, is its primary infection, and zoster (shingles) is its secondary
infection, caused by reactivation of VZV from latency. Varicella infection occurs in almost
all people over their lifetimes. VZV becomes latent after varicella and usually persists
silently and indefinitely. VZV reactivates, however, to cause zoster in roughly 20% of
individuals, with higher reactivation rates in immunocompromised patients and the
elderly.
Epidemiology
In the prevaccine era in the United States prior to 1995, approximately 4 million cases of
varicella and 1 million cases of zoster occurred annually. Varicella was primarily a disease of
children younger than age 10 years and zoster an illness of adulthood. Childhood varicella
infection, however, is less common than adult infection in countries that have tropical
climates. Varicella occurs in children who have no humoral or cellular immunity to VZV,
termed susceptibles. Zoster occurs in individuals who previously have had varicella; they
usually have detectable specific antibody titers, but have low or absent cell-mediated
immunity (CMI) to VZV.
VZV spreads primarily from the skin vesicles of persons who have varicella or zoster to
the respiratory tract of susceptible persons, who then become infected. Electron microscopic studies have shown a high concentration of well-formed, cell-free VZV in skin
vesicles. (1) Respiratory spread is difficult to rule out entirely, but during disease, it is rare
to isolate the virus from the throat, although it is common to isolate it from skin vesicles.
VZV spreads as cell-free enveloped viral particles, or virions, which are present in skin
vesicles and are small enough (approximately 200 nm in diameter) to be aerosolized. (2)
The virus spreads by the airborne route and requires direct exposure to an infected
individual for transmission.
Evidence for spread of VZV from skin is as follows. A 14% transmission rate of the
vaccine (Oka) strain of VZV occurred when susceptible siblings were exposed to a recently
immunized child who had leukemia and had a vaccine-associated rash. No transmission
occurred if the vaccinee had no rash, and VZV could not be isolated from the throats of any
of vaccinees, whether or not they had a vaccine-associated rash. Transmission rates were
directly proportional to the number of skin lesions. Recent observations in otherwise
healthy children who contracted wild-type breakthrough varicella after immunization also
have indicated that VZV spreads from skin. (3) Another recent study indicated that
*Professor of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY.
Pediatrics in Review Vol.29 No.1 January 2008 5
infectious diseases
varicella
The Diseases
Clinical Manifestations
Varicella usually is a mild-to-moderate illness in children.
It often is more severe in adults. Even in children, however, varicella cannot be counted on to be entirely benign. After a short or absent prodrome, skin lesions
appear. These start as macules and progress rapidly to
papules, vesicles, pustules, and scabs. The rash is concentrated on the trunk and head rather than on the extremities; it normally evolves as a series of successive crops
over 3 to 4 days. Most children have 250 to 500 superficial skin lesions, many of which are vesicular. Subclinical
elevations of hepatic transaminase concentrations are a
common, self-limited occurrence during varicella.
Zoster usually appears as a unilateral vesicular skin
eruption involving one to three dermatomes. Skin vesicles may be painful or pruritic, especially in adults. Zoster
generally is a milder disease in children than in adults.
From 25% to 50% of persons older than 50 years of age
and the same proportion of immunocompromised patients who acquire zoster experience serious pain, termed
post-herpetic neuralgia (PHN), after the rash has healed.
The cause of PHN is unknown.
Complications
The most common complication of varicella is bacterial
superinfection of the skin, lungs, or bones, most often by
Staphylococcus aureus or group A beta-hemolytic streptococci (GAS). Such infections may be severe and even
fatal. Whether treatment with ibuprofen is associated
with increased severity of GAS after varicella remains
unresolved. Therefore, this drug is not recommended for
treatment of fever accompanying varicella.
Central nervous system (CNS) complications, which
infectious diseases
may precede or follow varicella, include transient cerebellar ataxia, encephalitis, aseptic meningitis, and transverse myelitis. Most CNS complications are self-limited,
except for encephalitis, which frequently is associated
with severe sequelae if the patient survives. Other less
frequent complications of chickenpox include arthritis,
glomerulonephritis, myocarditis, and purpura fulminans.
Immunocompromised Patients
Varicella may be severe and even fatal in immunocompromised patients, particularly those who have malignancy or congenital deficits in CMI, as well as in those
who have undergone organ transplantation, have underlying HIV infection, or are receiving high doses of corticosteroids. Immunocompromised children who have severe varicella tend to have high fevers, extensive rashes
lasting for more than 1 week, hepatitis, and primary
viral pneumonia, which may be fatal despite antiviral
therapy. Children who have leukemia have a 30% rate of
disseminated varicella, with a 7% mortality rate. Severe
varicella may occur in HIV-infected children, especially
in those who have acquired immunodeficiency syndrome
(AIDS). In most of these children, however, mild-tomoderate varicella occurs, although the illness often is
more severe than occurs in healthy hosts.
Diagnosis
Chickenpox generally is diagnosed clinically because of
the characteristic vesicular rash and its distribution, as
well as through epidemiologic information such as history of exposure and absence of prior varicella. Zoster
also presents with a distinct unilateral, dermatomal, vesicular rash that is diagnosed clinically. Laboratory diagnosis can be used in questionable instances and is facilitated by the accessibility of the virus in superficial skin
lesions. (9) The diagnosis is made most definitively by
varicella
infectious diseases
varicella
Treatment
Nonspecific treatment for varicella includes oral antihistamines, frequent bathing, calamine lotion, oatmeal
baths, and the trimming of fingernails to discourage
scratching. Fever should be controlled with acetaminophen. Use of aspirin for this purpose may predispose to
Reye syndrome, and ibuprofen may predispose to GAS
infection.
Prevention
Control Measures
It virtually is impossible to protect susceptible individuals
from infection with VZV by avoidance because the agent
is highly communicable. Transmission is expected to
decrease, however, when VZV infection occurs in populations that are highly vaccinated.
Children who have chickenpox should be excluded
from school or child care from the time the diagnosis is
made until the lesions are crusted. Those who have zoster
may attend school if the lesions can be covered or when
they are crusted. The Table lists facts that can be helpful
in advising parents whose children are exposed to chickenpox. Patients who have active VZV infection and are
hospitalized should be isolated, preferably in a room that
has negative pressure ventilation, to minimize viral transmission.
Vaccination of individuals is particularly important if
there are family members who cannot be vaccinated,
such as a pregnant woman or immunocompromised
children. Transmission of the Oka strain from vaccinated
individuals, even if they develop a rash, is extremely rare
and has been reported after approximately 1 in 10 million
vaccinations.
Passive Immunization
Passive immunization is used to protect exposed highrisk persons from developing severe VZV. Treatment is
given to persons who have no history of previous VZV
disease, are at high risk for developing severe varicella,
infectious diseases
Table.
Active Immunization
Live attenuated varicella vaccine was developed in Japan
in 1974. (15) Since 1995, universal immunization of
healthy children and adults in the United States who are
susceptible to varicella has been recommended by the
Centers for Disease Control and Prevention (CDC).
This vaccine is extremely safe and well-tolerated. About
5% of healthy children develop a mild rash approximately
4 to 6 weeks after immunization. Serious neurologic
events have not been related causally to varicella vaccine.
Vaccinees who develop VZV rash within 2 to 3 weeks
varicella
infectious diseases
varicella
Summary
As a herpesvirus, VZV causes acute varicella, latent infection, and zoster. The virus has the potential to cause
serious infections, which may be difficult to treat. Complications include bacterial superinfections, CNS abnormalities, and a host of more unusual problems such as
pneumonia and hepatitis. Immunocompromised patients, pregnant women and their infants, and the elderly
are at highest risk of developing severe and even fatal
illnesses. In modern times, successful specific drug therapy has been developed. More recently, medical emphasis has been on prevention of illness by vaccination. Due
to the three-pronged approaches of passive immunization, active immunization, and antiviral therapy, the
morbidity and mortality from VZV infections have decreased impressively in the past 20 years. With continued
use and fine tuning of these modalities, particularly
active immunization, additional progress should be
made, resulting in the possibility of these infections
becoming unusual in the developed world.
References
1. Chen JJ, Zhu Z, Gershon AA, Gershon MD. Mannose
6-phosphate receptor dependence of varicella zoster virus infection
infectious diseases
varicella
PIR Quiz
Quiz also available online at www.pedsinreview.org.
1. Infections of susceptible persons with the wild-type varicella-zoster virus (VZV) are transmitted primarily
through:
A.
B.
C.
D.
E.
2. In a previously healthy 5-year-old child, the appearance of zoster most likely reflects a:
A.
B.
C.
D.
E.
3. A previously healthy 10-year-old boy develops uncomplicated varicella. As part of his initial management,
evidence-based practice supports the regular use of an appropriate dose of oral:
A.
B.
C.
D.
E.
Acetaminophen.
Acetylsalicylic acid.
Acyclovir.
Cephalexin.
Ibuprofen.
4. An 11-month-old girl who has acute lymphoblastic leukemia in early remission was inadvertently exposed
to varicella 1 day ago. To reduce the risk of life-threatening varicella, within 72 hours she should receive:
A.
B.
C.
D.
E.
5. You are asked to speak with a group of medical students about varicella vaccine. Your most appropriate
statement is that after initial immunization:
A.
B.
C.
D.
E.
Updated Information
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Reprints
Article
policy statements
American Academy of
Pediatrics Policy Statements
on Bioethics: Summaries and
Commentaries: Part 1
Mark R. Mercurio, MD,
Introduction
The American Academy of Pediatrics (AAP) has a strong and longstanding interest in the
field of bioethics and periodically publishes policy statements pertaining to specific ethical
questions relevant to pediatrics. The subjects addressed cover a wide range of topics, from
parental refusal of immunization to the care of critically ill children. These policies are
authored initially by the AAPs Committee on Bioethics and undergo extensive internal
review by other committees prior to publication.
This article is the first in a series of three intended to familiarize readers with many of the
AAP policies currently in place that address issues in bioethics. In this series, 16 policies
published by the AAP are summarized, each followed by a brief commentary. The
commentaries are intended to address, at least on a cursory level, some of the ethical
principles underlying the policies. Some briefly point out possible alternative viewpoints.
The policies referenced in this article represent the efforts of various committees and
committee members over the years. Each of the summaries presented here, as well as the
commentaries that follow, represents the work of individuals serving on the Executive
Committee of the Section on Bioethics, as indicated at the beginning of each summary.
Understandably, some of the wording of these summaries is taken directly from the
published policies. When quotations are used within a summary and not referenced, it can
be assumed that the quote is taken directly from the policy being summarized. For ease of
use, the references for each policy are provided with each individual summary and
commentary.
Author Disclosure
Drs Mercurio, Adam,
Forman, Ekman Ladd,
Friedman Ross, and
Silber did not disclose
any financial
relationships relevant
to this article.
Policies Reviewed
Part 1 of this series reviews:
1. Informed Consent, Parental Permission, and Assent in Pediatric Practice
2. Religious Objections to Medical Care
3. Responding to Parental Refusals of Immunization of Children
4. Sterilization of Minors With Developmental Disabilities
5. Human Embryo Research
Part 2 of this series reviews:
6. Guidelines on Foregoing Life-sustaining Medical Treatment
7. Foregoing Life-sustaining Medical Treatment in Abused Children
8. Do-Not-Resuscitate Orders for Pediatric Patients Who Require Anesthesia and
Surgery
9. Do-Not-Resuscitate Orders in Schools
10. Ethical Issues with Genetic Testing in Pediatrics
11. Ethics and Care of Critically Ill Infants and Children
Part 3 of this series reviews:
12. Female Genital Mutilation
13. Appropriate Boundaries in the Pediatrician-Family-Patient Relationship
14. Infants With Anencephaly as Organ Sources: Ethical Considerations
15. Palliative Care for Children
16. Institutional Ethics Committees
policy statements
bioethics
Comment
This policy, which provides for a genuine form of child
assent, is based clearly on Western values. Modeled after
the informed consent requirement for competent adult
patients, it takes seriously an ethical duty to keep the
child informed in age-appropriate ways and to solicit an
expression of the childs willingness (ie, assent), when
appropriate, to undergo the proposed treatment.
The policy is somewhat unclear about when it is
appropriate to solicit assent. Dissent may be ethically
binding in the case of nontherapeutic research or nonessential treatment, but the policy notes that it is deceptive to ask for assent when treatment is necessary and the
childs dissent will be overridden. On the other hand, it
seems to recommend solicitation of the childs willingness to accept treatment, even when it is deemed essential
and only parental permission is required, as one element
of involving the child in discussions about his or her
health care.
Asking the child for assent recognizes the dignity and
moral status of the child. The model is to provide a
gradually increasing involvement of the child in making
choices as the child grows in competence and moves
from complete dependency on parents to independence.
However, in our pluralistic society, the ideal of an individual as independent and free-thinking is not accepted
by all cultural groups. Some cultures expect decisions to
be made exclusively by parents or elders, whatever the
age of the younger generation. In addition, the idea of a
school-age child expressing an opinion at variance with
his or her parents may constitute an upheaval of traditional values when the parenting style is authoritarian.
In using the AAP policy, the pediatrician is following
Western democratic values and should be sensitive to the
fact that some families come from cultures that have
different views of the role of the child.
policy statements
Comment
An ethical justification for the AAP position on this
matter could be presented as a rights-based argument.
Every child, it could be argued, has a right to medical
care that is likely to prevent substantial harm or suffering or death. The childs right creates obligations for
the parents, the physician, and society. The parents are
obligated to bring the child for the needed treatment,
which, in the opinion of the AAP, cannot be limited to
prayer or other spiritual practices alone but should include appropriate medical care.
The physicians responsibility is either to provide the
necessary treatment if able or to attempt to procure
appropriate medical treatment for the child. The policy
states that the physician may withdraw from these cases if
continuing would violate his or her own moral precepts,
after securing acceptable alternative care. However, a
practitioner willing to withhold medical treatment likely
to prevent substantial harm would not seem to qualify as
a provider of acceptable alternative medical care.
bioethics
policy statements
bioethics
References
1. Walker v Superior Court, 763 P2d 852, 860 (Calif 1988), cert
denied. 1989; 491 US 905
2. Committee on Bioethics. American Academy of Pediatrics. Informed consent, parental permission, and assent in pediatric practice. Pediatrics. 1995;95:314 317
Comment
This statement takes an ethical and pragmatic position:
Encourage universal immunization because that practice
serves the childs best interest and because it promotes
herd immunity (community benefit), but respect refusals. The authors acknowledge that immunizations are
neither 100% safe nor 100% effective but argue that the
benefit-to-harm calculation is extremely high and justifies universal immunization policies and practices. The
e4 Pediatrics in Review Vol.29 No.1 January 2008
References
1. Salmon DA, Teret SP, MacIntyre CR, Salisbury D, Burgess MA,
Halsey NA. Compulsory vaccination and conscientious or philosophical exemptions: past, present, and future. Lancet. 2006;367:
436 442
2. Salmon DA, Moulton LH, Omer SB, DeHart MP, Stokley S,
Halsey NA. Factors associated with refusal of childhood vaccines
among parents of school-aged children: a case-control study. Arch
Pediatr Adolesc Med. 2005;159:470 476
3. American Academy of Pediatrics, Division of Health Policy
Research. Periodic Survey of Fellows No 48: Immunization Administration Practices. Elk Grove Village, Ill: American Academy of
Pediatrics; 2001
4. Flanagan-Klygis EA, Sharp L, Frader JE. Dismissing the family
who refuses vaccines: a study of pediatrician attitudes. Arch Pediatr
Adolesc Med. 2005;159:929 934
5. American Academy of Pediatrics Committee on Bioethics. Religious objections to medical care. Pediatrics. 1997;99:279 281
6. Goldstein J, Freud A, Solnit A. Before the Best Interests of the
Child. New York, NY: Free Press; 1979
policy statements
bioethics
Comment
This policy statement updates a previous AAP statement
entitled, Women Who Are Mentally Handicapped,
published in 1990. That statement was published as a
companion to a policy of the American College of Obstetricians & Gynecologists. The revised policy is based
on concepts developed in the earlier statements, but now
applies them to both males and females. This is the policy
to consult whenever parents or legal guardians approach
pediatricians or other health-care professionals about the
possibility of surgical sterilization of children, adolescents, and young adults who have developmental disabilities.
Sterilization has a long history of abuse in the United
States. However, by the middle of the 20th century, the
United States Supreme Court prompted a major change
in the legal landscape by declaring human procreation a
fundamental right. Since then, requests for authorization
to sterilize those who have developmental disabilities
have been the object of scrutiny, limitations, and even
prohibition in many jurisdictions. In the 1970s, for example, regulations were enacted to prevent the use of
federal funds to perform sterilization procedures on
those deemed mentally incompetent. It should come as
no surprise that, at present, we face so many federal rules,
state laws, and judicial rulings that pediatricians whose
advice is requested find themselves facing a confusing
and contradictory array of restrictions on surgical sterilization of persons with development disabilities. Indeed, this confusion may not be a coincidence because an
ethical tension exists between the obligation to honor
the least restrictive alternatives for those who have cognitive disabilities and the concern about abuse and coercion leading to unwanted pregnancy or, worse, a pregnancy that the child may not comprehend or may be
terrified by. Moreover, those who love and care for
developmentally delayed children certainly may have
their best interest at heart when they know that those
individuals are not capable of caring for offspring.
Although this statement gives guidance on how to
proceed when sterilization becomes the choice, its major
strength is that it develops the fundamental criteria required to make that decision ethically permissible,
namely, that the person lacks adequate mental capacity to
make decisions about his or her health care and is unable
to interpret his or her own interests. Thus, there is a
moral mandate before sterilization can be considered:
Assessment of an individuals capacity to decide matters
specifically concerning reproduction and an obligation to
obtain help from professionals experienced with evaluatPediatrics in Review Vol.29 No.1 January 2008 e5
policy statements
bioethics
Comment
The moral standing of the embryo has generated significant debate in the public sector, and this statement, not
surprisingly, created some controversy. Drs Chesney,
Botkin, and Nelson responded for the Committees on
Pediatric Research and Bioethics to a letter to the editor
of Pediatrics, stating, Given the fundamental disagreements over the moral status of embryos, it probably is
impossible to develop a position on this subject that all
would consider acceptable. (1) These fundamental disagreements are not scientific in origin because all parties
would agree that the human embryo is a being of human
policy statements
bioethics
References
1. Committee on Bioethics and Committee on Pediatric Research.
Embryonic stem cell research. Pediatrics. 2002;109:990 991
policy statements
bioethics
Conclusion
The AAP periodically publishes policy statements and
guidelines addressing difficult ethical issues that physicians caring for children will continue to face. This review
is intended to provide readers an overview of some of
those guidelines and possibly stimulate additional
thought and dialogue within the profession. It is presented by the AAP Section on Bioethics as part of its
mission to foster education in this area among pediatricians. As the commentaries suggest, there may not be
unanimity about the positions taken, which is important
to recognize. The full text of each policy, as well as other
relevant references and information, can be found on the
web site for the Section on Bioethics at http://
www.aap.org/sections/bioethics.
The Section on Bioethics serves primarily an educational role within the AAP and beyond. They organize
educational forums in bioethics at the annual AAP Na-