URINE ANTIGEN DETECTION OF BLASTOMYCOSIS
IN PEDIATRIC PATIENTS
Kanokporn Mongkolrattanothai, MD,* Milen Peev, MD,*
L. Joseph Wheat, MD,† and John Marcinak, MD*
Abstract: Blastomycosis is an uncommonly recognized disease in
pediatric patients. We describe 4 cases of pediatric blastomycosis
that presented to our children’s hospital, 2 with isolated pulmonary
blastomycosis and 2 with disseminated blastomycosis. Because of
variable clinical presentations and morbidity if treatment is delayed,
physicians must maintain a high index of suspicion and obtain
appropriate diagnostic tests promptly. For the first time, we report
the effect of therapy on Blastomyces antigen clearance. In our
experience, the urine antigen detection for B. dermatitidis is useful
for diagnosis and follow up during therapy.
Key Words: blastomycosis, urine antigen detection
From the *Section of Pediatric Infectious Diseases, Department of Pediatrics,
University of Chicago, Chicago, IL; and †MiraVista Diagnostics and
MiraBella Technologies, Indianapolis, IN.
Dr. Mongkolrattanothai is currently affiliated with the Section of Pediatric
Infectious Diseases, Department of Pediatrics, University of Illinois
College of Medicine at Peoria, Peoria, IL.
Address for correspondence: Kanokporn Mongkolrattanothai, MD, Section
of Pediatric Infectious Diseases, Department of Pediatrics, University of
Illinois College of Medicine at Peoria, 530 NE Glen Oak Avenue, Peoria,
IL 61637. E-mail email@example.com.
Copyright © 2006 by Lippincott Williams & Wilkins
the Mississippi and Ohio Rivers and the Great Lakes region. The
clinical presentations are highly variable ranging from asymptom-
atic, self-limited pulmonary infection to disseminated or even life-
threatening infection.1An important factor contributing to mortality
is a delay in diagnosis.2
Current diagnostic tests for the endemic mycoses, including
culture, serology and cytopathology, vary in their sensitivity and
specificity. Antigen detection offers a sensitive method for rapid
diagnosis of histoplasmosis.3–6Although much is known about
antigen detection in histoplasmosis, diagnosis of blastomycosis by
urine antigen detection was only first reported in 2004.7The purpose
of this article is to describe 4 cases of blastomycosis and our
experience with urine antigen detection for diagnosis and response
to antifungal therapy observed at our children’s hospital during a
lastomyces dermatitidis is endemic in the Southeastern, South
Central, and Midwestern states, especially in areas adjacent to
Case No. 1. A previously healthy 10-year-old black girl was admit-
ted to the University of Chicago Comer Children’s Hospital
(UCCH) for evaluation of fever and cough for 10 days. The family
history was notable for tuberculosis in the grandmother 4 years
earlier for which she completed a 6-month course of isoniazid and
rifampin-based therapy. Physical examination was significant for
decreased breath sounds over the right lower lung field. A chest
radiograph revealed a patchy air-space opacity of the right middle
lobe and lower lobe. She was treated with intravenous ceftriaxone
and oral azithromycin. A Streptococcus pneumoniae urine antigen
test was negative. Serum mycoplasma IgM on admission and 7 days
later was positive at 1:64 and 1:32, whereas Mycoplasma IgG was
negative on both days. The tuberculin skin test was placed twice and
was nonreactive. Although the patient demonstrated clinical im-
provement, she continued to have daily fevers.
On day 7 of hospitalization, a chest computed tomography
(CT) was obtained and revealed right lower lobe consolidation and
multiple 3- to 5-mm nodular opacities in the anterior segment of the
right upper lobe. Examination of the sputum specimens revealed a
few large broad-based budding yeasts on fungal smear and subse-
quent culture yielded B. dermatitidis. Sputum was negative by
acid-fast stain and by mycobacterial culture. Blastomyces antigen
was detected in urine, 3.30 enzyme immunoassay (EIA) units
(reference range: negative ?1.0 EIA units). She was treated with 10
mg/kg oral itraconazole per day and discharged 24 hours later.
Because she was unable to tolerate itraconazole orally, it was
administered intravenously and well tolerated. Patient received a
2-week course of intravenous itraconazole followed by oral itracon-
azole to complete a 6-month course.
Case No. 2. A previously healthy 14-year-old black boy was referred
because of fever, productive cough and shortness of breath for 4
weeks. Physical examination was notable for diminished breath
sounds bilaterally. A chest radiograph revealed diffuse pulmonary
interstitial disease. A chest CT showed diffuse interstitial and
air-space consolidation throughout the left upper lobe and right
middle lobe. Sputum specimens were negative on fungal and acid-
fast smears. Sputum culture yielded B. dermatitidis. Antibodies to B.
dermatitidis were not detected either by complement fixation or
immunodiffusion tests. Nevertheless, a serologic test was positive
for Histoplasma capsulatum by complement fixation test using yeast
and mycelial antigen. Blastomyces antigen in urine was elevated at
3.01 EIA units as was Histoplasma antigen at 3.56 EIA units. He
was treated with 200 mg oral itraconazole twice daily (5 mg/kg per
day). Follow up at 6, 16 and 68 weeks demonstrated a decrease in
urine antigen (Fig. 1). He completed a 6-month course of therapy. At
a follow-up clinic visit 9 months after itraconazole had been dis-
continued, the patient was asymptomatic.
Case No. 3. A 17-year-old black boy with a history of sinus
histiocytosis with lymphadenopathy presented because of a 4-week
history of fever, cough, skin lesions and a 6-pound weight loss.
Physical examination was remarkable for decreased breath sounds
over the right lower lung field. There were also 2 2 ? 3-cm soft,
tender, erythematous nodules over the lateral aspect of elbow. A
chest radiograph revealed a right lower lobe air-space disease and
right hilar adenopathy. Ultrasonography of the right antecubital
fossa demonstrated an ovoid multiseptate fluid collection. Fluid
aspiration of the skin lesion was negative by Fram, acid-fast and
fungal stains. The culture subsequently yielded B. dermatitidis.
Serologic tests for antibodies to B. dermatitidis were positive by
immunodiffusion but negative by complement fixation. Urine anti-
gen tests for blastomycosis and histoplasmosis 4 days before hos-
pital admission were positive at 16.85 and 8.38 EIA units, respec-
tively. He was admitted and treated with amphotericin B for 2 weeks
and subsequently received a 12-month course of itraconazole in a
dosage of 100 mg twice daily. He had resolution of the pneumonia
as well as all of the skin lesions. Follow up demonstrated a
decreased in antigenuria (Fig. 1).
Case No. 4. A 14-year-old black girl was referred for evaluation of
back pain. There was a 4-week history of fever up to 104°F, right
fourth-digit swelling and 30-pound weight loss. On physical exam-
ination, she appeared to be in respiratory distress and required
oxygen supplement because of low arterial oxygen saturation on
room air (88%). She had a 2-cm open, draining skin wound on the
back of the left shoulder as well as 1 ? 1-cm nodules over her arm,
leg and trunk. She was admitted to the intensive care unit for
management of respiratory distress.
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The Pediatric Infectious Disease Journal • Volume 25, Number 11, November 2006
A chest radiograph showed a diffuse reticulonodular infiltrate.
Magnetic resonance imaging (MRI) of the thoracic and lumbar spine
showed a paravertebral abscess at L5–S1 and osteomyelitis involv-
ing T12, S1–S2 vertebral bodies and the right iliac bone. A skin
biopsy was performed and revealed broad-based budding yeasts on
fungal smear that was morphologically consistent with B. dermati-
tidis. The sputum was negative by smear for acid-fast bacilli and
fungi. The sputum and skin biopsy grew B. dermatitidis. Blastomy-
ces antigen in urine was elevated at 54.73 EIA units and His-
toplasma antigen at 31.91 EIA units. Serologic tests, including
blastomycosis and histoplasmosis complement fixation and immu-
nodiffusion, were negative. The patient was treated with 1 mg/kg
amphotericin B per day for 2 weeks followed by 100 mg oral
itraconazole twice a day.
The patient was nonadherent with therapy. Four months later,
she was readmitted because of swelling of her right fourth digit. The
Blastomyces antigen in urine remained elevated at 50.46 EIA units.
A skin biopsy culture of the finger again grew B. dermatitidis. A
plain radiograph of the hand showed a diffuse destructive lesion of
the proximal and middle phalanx. Amphotericin B was restarted but
switched to amphotericin B lipid complex because of a rise in serum
creatinine (2.5 mg/dL). Amphotericin B lipid complex was admin-
istered for 6 weeks followed by 200 mg itraconazole twice daily.
The swelling of the finger decreased significantly. Follow-up MRI of
the spine showed resolution of the paravertebral abscess and de-
crease in signal intensity of the right sacral and iliac bones. Anti-
genuria declined but did not clear as of 17 months of follow up after
the initial diagnosis (Fig. 1). The patient continues to have a flexion
deformity of the right fourth digit at 7 months of follow up after the
Blastomycosis is uncommonly reported8,9in children but can
cause severe illness associated with morbidity and occasionally
mortality as a result of a delay in diagnosis. Pulmonary blastomy-
cosis can manifest as an asymptomatic lung infiltrate, acute or
chronic pneumonia or even life-threatening illness such as acute
respiratory distress syndrome (ARDS).10,11
In case no. 1, the child was initially misdiagnosed as having
acute bacterial pneumonia and was managed with antimicrobial
therapy. She failed to defervesce despite appropriate antimicrobial
therapy for community-acquired pneumonia. Possible complications
of pneumonia, for instance, parapneumonic effusion or empyema as
well as resistant or unusual pathogens, were actively sought. This
case highlights the importance of prompt recognition and the diag-
nosis should be actively pursued through microbiologic and/or
The diagnosis of blastomycosis can be confirmed by identi-
fying B. dermatitidis in tissue or body fluids by microscopy and/or
culture. Visualization of the characteristic broad-based budding
yeast form on tissue examination can make a presumptive diagnosis.
In one report, cytology of respiratory secretions provided the initial
basis for diagnosis in 58% of cases and was positive in 93%.12
However, in our case series, only one of 3 patients who had a fungal
smear of sputum sent for diagnosis had a positive result, whereas all
cases were confirmed by culture. Standard culture-based fungal
identification requires as long as 3 to 4 weeks, resulting in a delayed
Antigen testing has been used to provide a rapid diagnosis of
disseminated histoplasmosis.3–6Also, the level of antigen can be
used to follow the effect of therapy with reduction to undetectable in
successful therapy or rising in antigen suggesting relapse or treat-
ment failure.4,6However, limited data are available about the anti-
gen testing in blastomycosis. Of note, antigenuria was present in all
4 of our patients. The diagnosis of pulmonary or disseminated
blastomycosis by urine antigen detection is promising and could
play a major role in a rapid diagnosis of blastomycosis.7The test had
high sensitivity (92.9%) but moderate specificity (79.3%) because of
crossreactivity with other endemic mycoses such as histoplasmosis
(96.3%) and paracoccidioidomycosis (100%). This finding is illus-
trated by our case nos. 2, 3 and 4 in which the Histoplasma antigen
test was positive before culture confirmation of the diagnosis of
The Blastomyces urine antigen test also could be useful for
following the response to therapy because clearance of antigen
correlated well with successful therapy and clinical improvement
seen in 3 of 4 cases. This is the first demonstration of Blastomyces
antigen clearance during therapy and the findings are similar to those
reported in histoplasmosis. Failure of antigenuria to clear was a clue
to treatment failure in case no. 4. Further prospective studies are
warranted to validate the use of antigen detection for diagnosis and
follow up of blastomycosis.
The authors acknowledge Dr. Robert Daum for his thoughtful
review of the manuscript. The authors thank Jennifer Burns, PNP,
and members of the house staff of the University of Chicago Comer
Children’s Hospital for taking care of the patients.
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FIGURE 1. Clearance of Blastomyces antigenuria during anti-
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Mongkolrattanothai et al
The Pediatric Infectious Disease Journal • Volume 25, Number 11, November 2006
© 2006 Lippincott Williams & Wilkins
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