746 Part XIV Immunology

neutrophil apoptosis and subsequent clearance of degenerating

neutrophils by macrophages, which in turn leads to ongoing local
tissue damage from release of proteases and other granule
proteins.

Clinical Manifestations
Although the clinical presentation is variable, several features
suggest the diagnosis of CGD. Any patient with recurrent pneumonia, lymphadenitis, hepatic or other abscesses, osteomyelitis
at multiple sites, a family history of recurrent infections, or any
infection with an unusual catalase-positive organism requires
evaluation. Residual NADPH oxidase may attenuate CGD.
The onset of clinical signs and symptoms may occur from early
infancy to young adulthood. The attack rate and severity of infections are exceedingly variable. The most common pathogen is S.
aureus, although any catalase-positive microorganism may be
involved. Other organisms frequently causing infections include
Serratia marcescens, Burkholderia cepacia, Aspergillus, Candida
albicans, Nocardia, and Salmonella. There may also be increased
susceptibility to mycobacterium including the BCG vaccine.
Pneumonia, lymphadenitis, osteomyelitis, and skin infections are
the most common illnesses encountered. Bacteremia or fungemia
occur but are much less common than focal infections. Patients
may suffer from the sequelae of chronic infection, including
anemia of chronic disease, poor growth, lymphadenopathy,
hepatosplenomegaly, chronic purulent dermatitis, restrictive lung
disease, gingivitis, hydronephrosis, and pyloric outlet narrowing.
Perirectal abscesses and recurrent skin infections, including folliculitis, cutaneous granulomas, and discoid lupus erythematosus
also suggest the possibility of CGD. Granuloma formation and
inammatory processes are a hallmark of CGD and may be the
presenting symptoms that prompt testing for CGD if they cause
pyloric outlet obstruction, bladder outlet or ureter obstruction,
or rectal stulae and granulomatous colitis simulating Crohn
disease.

prednisone (0.5 mg/kg/day); treatment should be tapered over

several weeks. Inhibitors of tumor necrosis factor alpha pathways, such as iniximab, should be avoided if possible due to the
very high risk of invasive fungal infection.
Interferon- (IFN-) 50 g/m2 3 times/wk reduces the number
of hospitalizations and serious infections. The mechanism of
action of IFN- therapy in CGD is unknown. Itraconazole
(200 mg/day for patients >50 kg and 100 mg/day for patients
<50 kg and 5 yr of age) administered prophylactically reduces
the frequency of fungal infections.

Genetic Counseling
Identifying a patients specic genetic subgroup is useful primarily
for genetic counseling and prenatal diagnosis. In cases of suspected X-linked CGD, further analysis is not necessary if the fetus
is initially demonstrated to be a 46,XX female. Fetal blood sampling and oxidase function analysis of fetal neutrophils can be
used for prenatal diagnosis of CGD. DNA analysis of amniotic
uid cells or chorionic villus biopsy is an option for early prenatal
diagnosis in families in which the specic mutation is known.

Prognosis
The overall mortality rate for CGD is about 2 patient deaths/
yr/100 cases, with the highest mortality among young children.
The development of effective infection prophylactic regimens,
close surveillance for signs of infections, and aggressive surgical
and medical interventions has improved the prognosis.
BIBLIOGRAPHY
Please visit the Nelson Textbook of Pediatrics website at www.expertconsult.
com for the complete bibliography.

Chapter 125

Laboratory Findings

Leukopenia

The diagnosis is most often made by performing ow cytometry

using dihydrorhodamine 123 (DHR) to measure oxidant production through its increased uorescence when oxidized by H2O2.
The nitroblue tetrazolium (NBT) dye test is frequently cited in
the literature but is now only rarely used clinically.
A few individuals have been described with apparent CGD
due to severe glucose-6-phosphate dehydrogenase (G6PD) deciency, leading to insufcient NADPH substrate for the phagocyte
oxidase. The erythrocytes of these patients also lack the enzyme,
leading to chronic hemolysis.

Peter E. Newburger and Laurence A. Boxer

Treatment
HSCT is the only known cure for CGD. For supportive care,
patients with CGD should be given daily oral trimethoprimsulfamethoxazole and an antifungal drug, such as itraconazole
(see later), for prophylaxis of infections. Cultures must be
obtained as soon as infection is suspected. Most abscesses require
surgical drainage for therapeutic and diagnostic purposes. Prolonged use of antibiotics is often required. Aspergillus or Candida
infection requires treatment with intravenous antifungal drugs.
Granulocyte transfusions may be necessary if antibiotics are ineffective. If fever occurs without an obvious focus, it is advisable
to consider the use of radiographs of the chest and skeleton as
well as CT scans of the liver to determine if pneumonia, osteomyelitis, or liver abscesses are present. The cause of fever cannot
always be established, and empirical treatment with broad-spectrum parenteral antibiotics is often required. The erythrocyte
sedimentation rate (ESR) may be used to help determine the duration of antibiotic treatment.
Corticosteroids may also be useful for the treatment of
children with antral and urethral obstruction or severe granulomatous colitis. Granulomas may be sensitive to low doses of

Marked developmental changes in normal values for the total

white blood cell (WBC) count occur during childhood (Chapter
708). The mean WBC count at birth is high, followed by a rapid
fall beginning at 12 hr until the end of the 1st wk. Thereafter,
values are stable until 1 yr of age. A slow, steady decline in the
WBC count continues throughout childhood until reaching the
adult value during adolescence. Leukopenia in adolescents and
adults is dened as a total WBC count <4,000/L. Evaluation of
patients with leukopenia, neutropenia, or lymphopenia begins
with a thorough history, physical examination, family history,
and screening laboratory tests (Table 125-1).

NEUTROPENIA
Neutropenia is an absolute neutrophil count (ANC), calculated
as the WBC count % of neutrophils and bands, more than 2
standard deviations below the normal mean. Normal neutrophil
counts must be stratied for age and race. For whites over the
age of 12 mo, the lower limit of normal for the neutrophil count
is 1,500/L, and for blacks over 12 mo old, the lower limit of
normal is 1,200/L. The relatively lower limit in blacks probably
reects a relative decrease in neutrophils in the storage compartment of the bone marrow. Neutropenia may be characterized as
mild neutropenia, with an ANC of 1,000-1,500/L; moderate
neutropenia, with an ANC of 500-1,000/L; or severe neutropenia, with an ANC <500/L. This stratication aids in predicting the risk of pyogenic infection; only patients with severe
neutropenia have signicantly increased susceptibility to lifethreatening infections.