574082

research-article2015

CPJXXX10.1177/0009922815574082Clinical PediatricsBidadi et al

Resident Rounds

Adolescent With Lymphadenopathy in

the Absence of Systemic Symptoms

Clinical Pediatrics
2015, Vol. 54(12) 12211223
The Author(s) 2015
Reprints and permissions:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0009922815574082
cpj.sagepub.com

Behzad Bidadi, MD1, Adaora S. Uzodi, MBBS2,

Bobbi S. Pritt, MD3, Shakila P. Khan, MD4, and
Nancy K. Henry, MD, PhD5
Case Report
A 17-year-old adolescent male from Saudi Arabia presented to us for evaluation of abdominal and cervical
lymphadenopathy. The patient was previously healthy
until 5 months prior to presentation when he developed
radiating lumbar pain. Worsening pain associated with
difficulty ambulating prompted a spine magnetic resonance imaging at an outside institution which revealed
disk protrusion at L4-L5. His back pain spontaneously
resolved within 1 month. However, the spine MRI demonstrated an incidental finding of mesenteric lymphadenopathy. He denied any systemic symptoms.
He was referred to a hematologist in Saudi Arabia and
computed tomographic imaging revealed splenomegaly
as well as mildly enlarged cervical, abdominal, pelvic,
and inguinal lymph nodes. His C-reactive protein (CRP)
was elevated at 17 mg/L and erythrocyte sedimentation
rate (ESR) was also high at 31 mm/h. His white blood
cell count was 8900 cells/mm3 with 57% neutrophils. He
underwent an open biopsy of one of the enlarged mesenteric lymph nodes and a pathologic diagnosis of follicular hyperplasia was made. To explore the etiology of
these findings, serologies for HIV, Toxoplasma gondii,
and Brucella spp were performed and were negative.
QuantiFERON-TB testing was negative. His lymphadenopathy was diagnosed as reactive without an identifiable etiology.
The family was concerned for a serious systemic disease so they sought a second opinion at our institution. At
the time of our evaluation, he was asymptomatic other
than the recent onset of upper respiratory symptoms. He
had a mild cough that improved over several days without antimicrobial intervention. He reported that he had
exposure to horses and he periodically drank unpasteurized goats milk. His physical examination was unremarkable other than shotty cervical lymphadenopathy.
Our laboratory evaluation revealed a white blood cell
count was 7400/mm3 with 48% neutrophils. He had a mild
microcytic hypochromic anemia with hemoglobin of 12.3
g/dL and mean corpuscular volume of 74.2 fL. Ferritin was
normal at 25 g/L. Liver function tests were within normal
limits (alanine transaminase 21 U/L, aspartate transaminase

21 U/L, alkaline phosphatase 118 U/L, total and direct bilirubin of 0.3 mg/dL and 0.1 mg/dL, respectively). The ESR
was normal at 12 mm/h but CRP was elevated at 23.3 mg/L.
A CRP performed 4 days later was 10.2 mg/L, coincident
with resolution of his upper respiratory symptoms. This
near normalization suggests CRP elevation was related to
his upper respiratory symptoms. Review of the original
computed tomographic imaging confirmed mild enlargement of the spleen as well as abdominal, pelvic and inguinal
lymph nodes.
Serologies for HIV, Bartonella spp, Leishmania spp,
Toxoplasma gondii, and Epstein-Barr virus were negative
with normal immunoglobulin levels. QuantiFERON-TB
testing was negative. Cytomegalovirus testing revealed
negative IgM with positive IgG consistent with past infection. A Brucella spp serology showed a negative IgM but
positive IgG. This was confirmed with an elevated serum
agglutination titer of 1:320 (reference 1:80). Pathologist
review at Mayo Clinic of the original lymph node biopsy
revealed follicular lymphoid hyperplasia, monocytoid
B-cell hyperplasia, and focal clusters of epithelioid histiocytes encroaching on follicle centers.

Hospital Course
Despite the absence of systemic symptoms, the history of
generalized lymphadenopathy, ingestion of unpasteurized
1

Division of Pediatric Hematology Oncology, Department of

Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN,
USA
2
Division of Pediatric Infectious Diseases, Department of Pediatrics
and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
3
Division of Clinical Microbiology, Department of Laboratory
Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
4
Division of Pediatric Hematology Oncology, Department of
Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN,
USA
5
Division of Pediatric Infectious Diseases, Department of Pediatrics
and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
Corresponding Author:
Behzad Bidadi, Division of Pediatric Hematology Oncology,
Department of Pediatrics and Adolescent Medicine, Mayo Clinic,
200 1st Street SW, Rochester, MN 55905, USA.
Email: bidadi.behzad@mayo.edu

1222

Figure 1. Gram-negative coccobacilli (central cluster) seen

against the granular background of a blood culture bottle
(gram stain, magnification 1000).

milk, and positive Brucella IgG titers led us to obtain blood

cultures for Brucella spp. One of 4 culture bottles grew
Brucella that was identified by the Minnesota Department
of Health as Brucella melitensis (Figure 1). Warthin-Starry
and gram stains were later performed on his lymph node
tissue. Gram stain was unrevealing but the Warthin-Starry
stain revealed the presence of coccobacilli including some
visualized within macrophages (Figure 2) confirming the
etiology of our patients lymphadenopathy.
He was treated with a 6-week course of trimethoprimsulfamethoxazole, 1 double-strength tablet (800 mg sulfamethoxazole160 mg trimethoprim) orally once daily
and rifampin 600 mg orally once daily. An outside institution in Saudi Arabia obtained a follow-up Brucella
serology 5 months after his diagnosis, which showed an
IgG level of 1:640. Repeat computed tomography imaging of the chest, abdomen, and pelvis demonstrated stable generalized lymphadenopathy. He returned for
follow-up at our hospital three months later at which
time repeat Brucella serology and Brucella blood cultures were negative. He remained free of systemic
symptoms.

Final Diagnosis
Brucellosis.

Discussion
Brucellosis (also known as Mediterranean fever, undulant fever) is the most common zoonotic disease worldwide. More than half a million cases are reported
annually.1 It is caused by Brucella spp, which are
small, gram-negative, aerobic, facultative intracellular

Clinical Pediatrics 54(12)

Figure 2. Warthin-Starry stain highlights clusters of

organisms (arrows) consistent with Brucella (magnification
1000).

coccobacilli. Most cases of brucellosis are caused by

Brucella melitensis. Brucellosis has a worldwide distribution but is endemic in parts of the Middle East,
Asia, Central and South America, and Eastern Europe.
Incidence in the United States is low; about 80 to 140
cases reported annually.2 In most cases, there is a history of ingestion of unpasteurized milk or direct contact with infected animals.
Brucellosis is a systemic illness that can affect any
organ. The clinical presentation of brucellosis is quite
variable which often delays the diagnosis. Fever is present in 80% to 100% of children3,4 and malaise in more
than 50%.4 Other common findings at presentation
include constitutional symptoms and arthritis. Findings
on physical exam are usually nonspecific and include
hepatosplenomegaly and lymphadenopathy. Patients
can also frequently have back pain but this is most frequently related to sacroiliitis and spondylitis.
Asymptomatic brucellosis diagnosed by seropositivity is not uncommon and known to occur in household
contacts of patients with brucellosis.5 Brucella spp seropositivity in otherwise asymptomatic patients has been
reported with differing rates based on the geographic
region. A report of 25 acute brucellosis patients5 identified asymptomatic family members who were seropositive. Of the 178 family members tested, 40 (23%) had
various symptoms while 11 members were asymptomatic (8%).
Approximately 10% of brucellosis patients develop
lymphadenopathy.1 Lymphadenopathy as the sole manifestation of brucellosis has been described in a small
number of case reports in which the patients had associated supparative lymphadenitis.6-8 All these reports
describe isolated cervical lymph node involvement.

1223

Bidadi et al
These patients also differ from our case considering they
had suppurative lymphadenitis.
Brucella spp bacteremia in asymptomatic individuals is
quite rare or underreported. Evaluation of household
members of a 10-year-old boy with brucellosis yielded
positive Brucella melitensis blood cultures in 2 otherwise
asymptomatic patients.9 The authors of this report note
that this is the first report of brucellosis made in asymptomatic individuals with positive Brucella blood cultures.
A review of 100 culture positive cases of brucellosis at a
single institution yielded 6 atypical cases of brucellosis
that would otherwise have not been found.10 These patients
had unusual presentations of brucellosis. The authors
argue that the routine screening of all patients with
Brucella blood cultures is how brucellosis was diagnosed.
Our case is similar to the aforementioned reports considering our patient had Brucella melitensis bacteremia from an
endemic region with no systemic symptoms.
The diagnosis of brucellosis in our patient was definitive. Brucella melitensis was isolated from blood culture. Warthin-Starry staining identified the organism in a
lymph node biopsy. Serologic testing was consistent
with infection with Brucella spp. The recommended
treatment for uncomplicated brucellosis in children at
least 8 years of age is a 6-week course of combination
therapy using rifampin with trimethoprim-sulfamethoxazole or an oral tetracycline. Our patient received
rifampin and trimethoprim-sulfamethoxazole with good
response evidenced by clearance of bacteremia and a
decline in Brucella titers from 1:640 to negative values.
The patient and his family were cautioned regarding the
risk of brucellosis associated with unpasteurized milk.
Our patient had chronic back pain, which raised suspicion for spondylitis or sacroiliitis secondary to brucellosis. Orthopedic consultation and review of imaging
studies of the spine attributed this to lumbar disk protrusion. We postulate this was not related to brucellosis
because he had no imaging findings characteristic of
spondylitis and it resolved before his brucellosis was
adequately treated. Diskitis in the absence of spondylitis
secondary to brucellosis has been reported but is exceedingly rare.11 The only clinical manifestation that we can
attribute to brucellosis are his lymphadenopathy and
splenomegaly. The laboratory abnormalities of anemia
and mild CRP and ESR elevations are compatible with
brucellosis.

Conclusions
This case highlights the importance of considering brucellosis in the differential diagnosis of lymphadenopathy in a patient from an endemic region even in the
absence of constitutional symptoms. It stresses the utility of obtaining Brucella spp blood cultures when the

diagnosis is suspected as patients with brucellosis can be

asymptomatic even in the presence of bacteremia. When
brucellosis is suspected, it is important to notify the
microbiology lab so that the correct testing can be performed and patients can be appropriately treated.
Author Contributions
All authors substantially contributed to the conception and
design of this manuscript. BB and ASU drafted the manuscript. All authors critically revised the manuscript and have
given their final approval.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.

Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.

References
1. Franco MP, Mulder M, Gilman RH, Smits HL. Human
brucellosis. Lancet Infect Dis. 2007;7:775-786.
2. Centers for Disease Control and Prevention. Brucellosis
surveillance. http://www.cdc.gov/brucellosis/resources/
surveillance.html. 2012. Accessed November 8, 2013.
3. Benjamin B, Annobil SH. Childhood brucellosis in
southwestern Saudi Arabia: a 5-year experience. J Trop
Pediatr. 1992;38:167-172.
4. al-Eissa YA, Kambal AM, al-Nasser MN, al-Habib SA,
al-Fawaz IM, al-Zamil FA. Childhood brucellosis: a study
of 102 cases. Pediatr Infect Dis J. 1990;9:74-79.
5. Almuneef M, Memish ZA, Al Shaalan M, Al Banyan E,
Al-Alola S, Balkhy HH. Brucella melitensis bacteremia in
children: review of 62 cases. J Chemother. 2003;15:76-80.
6. zhan B, Kamit F, Akduman , Ay Y, Helvac M. A
rare manifestation of brucellosis: cervical lymphadenitis.
ocuk Enfeksiyon Dergisi. 2009;3:190-191.
7. Varona JF, Guerra JM, Guillen V, Guillen S, Menassa
A, Palenque E. Isolated cervical lymphadenopathy as
unique manifestation of brucellosis. Scand J Infect Dis.
2002;34:538-540.
8. Nadler H, Dolan C, Forgacs P, George H. Brucella suis:
an unusual cause of suppurative lymphadenitis in an outpatient. J Clin Microbiol. 1982;16:575-576.
9. Celebi G, Kulah C, Kilic S, Ustundag G. Asymptomatic
Brucella bacteraemia and isolation of Brucella melitensis biovar 3 from human breast milk. Scand J Infect Dis.
2007;39:205-208.
10. Jayakumar RV, Al-Aska AK, Subesinghe N, Wright

SG. Unusual presentation of culture positive brucellosis.
Postgrad Med J. 1988;64:118-120.
11. Demirci I. Brucella diskitis mimicking herniation without spondylitis; MRI findings. Zentralbl Neurochir.
2003;64:178-181.

Copyright of Clinical Pediatrics is the property of Sage Publications Inc. and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.