Z Orbak, H Tan, MD, O Ziraaatci, A Turgut, N
Gursan, H Alp, C Karakelleoglu
Departments of Pediatrics and Pathology, Atatürk University Faculty of
Medicine, Erzurum, Turkey
Correspondence: Dr. Zerrin Orbak, Atatürk Üniversitesi Dis Hekimligi Fakültesi, Periodontoloji Anabilim Dali, 25240 Erzurum, Türkiye
SMJ 2008 53(2): 66
Abstract
This report details the clinical and
histopathological characteristics and course of glandular tularemia, an uncommon
but significant cause of cervical lymphadenopathy in two children. Tularemia
should be considered in the differential diagnosis of cases with
non-tuberculosis, suppurative cervical lymphadenopathy, particularly in those
not responding to penicillin treatment.
Introduction
Children with infectious cervical lymphadenopathy are frequently seen by pediatricians and hemato-oncologists. The etiologic agents in most cases are commonplace, and the diagnosis and treatment are simple and uncomplicated. But some rare cases require a more comprehensive approach to identification of the etiologic agent and the attention of a surgical specialist for biopsy or incision and drainage of an abscess.
One significant but uncommon cause of cervical lymphadenopathy in children is glandular tularemia. The causative agent of the disease tularemia is Francisella tularensis, a non-capsulated, gram-negative coccobacillus and zoonotic bacteria. It is of interest for several reasons. First, making a definitive microbiologic identification of F tularensis is challenging because of its fastidious growth characteristics and potential hazard to laboratory workers (1). Moreover, F tularensis is considered to be a potential bioterrorism agent because of its extreme virulence, its ease of dissemination, transmissibility as an aerosolized agent, and its capacity to cause severe illness and death (1, 2). F tularensis was believed to cause severe disease in mammals and mild to rapidly progressive and fatal systemic disease in humans (2). The risk of morbidity and mortality in patients with glandular tularemia is best minimized by specific antimicrobial therapy that is not usually considered for the more common causes of infectious lymphadenopathy (1)
In
this article, we describe two cases who presented with suppurative cervical
lymphadenitis. Clinical, laboratory and histopathological charecteristics of
this disease as well as the response to medical therapy are discussed with a
review of the worl literature.
Case 1
A 5.5-year-old boy was admitted to our clinic
for evaluation of a three-month- history of neck masses. First, right-sided
cervical lymph node has enlarged, suppurated and developed scar 15-day after
treatment with amoxicillin. The following week, left-sided mass has developed
and he has been referred our clinic. His medical history was unremarkable, and
his immunization were unknown (scar for tuberculosis was negative). He live in
farm. There was no history of specific tick or insect bite and any knowledge of
contact the primary vectors in zoonotic transmission was denied. Examination
there revealed that the 5 x 2.5-cm suppurative lymphadenopathy was located to
the left posterior sternocleidomastoid muscle (Figure 1a). There was the 1 x
1-cm scar lesion on the right anterior sternocleidomastoid muscle related to
improved lympadenopahty in history (Figure 1b). Findings on the remainder of the
physical examination were unremarkable. Laboratory studies revealed that his
white blood cell count was 7.200/mm3, his segmented neutrophil level
was 60%, his band neutrıphil level was 8%, his lymphocyte level was 32%.
Erythrocyte sedimentation rate was 35 mm/h. C-reactive protein was slightly
high. The serum electrolytes and liver and kidney function tests were normal.
We
performed biopsy of the neck mass. The widespread necrotizing acute inflammation
was shown in histopathologic analysis (Figure 2a). One week after surgery, a
reference laboratory reported a significant high antibody level
to F. Tularensis in the
serologic examination (1:180).
The
patient was treated with IV gentamicin at 80 mg every 12 hours for 2 weeks, and
his symptoms resolved completely with scar lesion (Figure 1c). At the 6-monyh
follow-up, he showed no sign of recurrence.
Case 2
A 10-year old boy was brought to a physician
with symptoms of an upper respiratory tract infection, fever and right upper
cervical swelling. Oral penicilline and acetaminophen treatment was prescribed.
By the time he came to our clinic, he had completed 10-day antibiotic regimen
but showed no sign of improvement. Phisical examination revealed that he had a 5
x 6-cm infraauricular mass, which was characterized by suppuration, tenderness,
and local edema. The patients skin, scalp, and oropharynx exhibited no sign.
Findings on the remainder of the physical examination were normal. Laboratory
studies revealed that his white blood cell count was 7.800/mm3, his
segmented neutrophil level was 60%, his band neutrıphil level was 4%, his
lymphocyte level was 36%. Erythrocyte sedimentation rate was 26 mm/h. The serum
electrolytes and liver and kidney function tests were normal. On doppler
ultrasonography of cervical area demonstrated a 42 x 23-mm necrotizing
lymphadenopathy.
His
medical history was unremarkable, and his immunization were completed. There was
no history of specific tick or insect bite and any knowledge of contact the
primary vectors in zoonotic transmission was denied. He lives in rural area.
At the completion of the antibiotic therapy,
the patient had still not shown any improvement. Excisional biopsy was performed
for histologic examination. Histopatholigic examination showed the widespread
necrotizing acute inflammation (Figure 2b). Also, It was observed that presence
of antibodies at a significant level to F.
Tularensis in the serologic examination (1:160).
The
patient was treated with IV gentamicin at 100 mg every 12 hours, and his
symptoms resolved completely. The patient completed a 2-week course of
gentamicin without complication or further symptoms. At the 6-monyh follow-up,
he showed no sign of recurrence.
Discussion
Glandular tularemia is one of clinical
syndromes in humans that manifest as infection by F. Tularensis; these formes are distinguished by their mode of
transmission and portal of pathogen entry (1). Tularemia is almost exclusively a
rural disease. The incidence of tularemia has declined markedly from thousands
of cases per year during the first half of the 20th century to
hundreds of cases annually since 1950 (3, 4).
F. Tularensis
survives in rodents such as rabbits, mice and squirrels, in ticks and rarely in
animals such as calves, cats and dogs (5). Blood-sucking arthropods and insects
are most important host vectors. The microorganism is transmitted animals or
their tissues, by eating them, by inhalation of dust contaminated by the feces
of infected arthropods or by drinking contaminated water (5, 6). A history of
tick exposure is frequently not available (4) like our patients.
The
incubation period of the disease is 2 to 6 days (range: 1 to 20 days) (5). It is
characterized by general symptoms such as fever, headache, sore throat, malaise,
myalgias, cough and cutanous lesions. No clinical signs develop in nearly half
of the infected person. The main signs are pharyngotonsillitis and servical
lymphadenitis (5). The majority of these patients are nonspecific in their
initial clinical and laboratory presentation and may be confused with a variety
of more common illnesses. Clinical suspicion are of key importance in making the
appropriate diagnosis. Early and specific therapy is a principal factor in
reducing the morbidity and mortality associated with tularemia.
The
imaging features of tularemia are non-specific. Enlarged nodes and nodes with
central necrosis are well demonstrated by MRI (5, 7). In our second patient,
enlarged necrotic lymph node was demonstrated by doppler ultrasonography. We
could not find any knowledge about evaluating lymph nodes by ultrasonography.
In
the pathologic examination of the lymph nodes, chronic granulomatous-type
inflammation is observed in tularemia. Lesions are characterized by the
surrounding epitheloid histiocysts, macrophages, lymphocyts and, on occasion,
giant cells, in addition to necrosis regions in the central area. In time, a
part of these lymph nodes becomes abscessed with necrosis and has to be drained
(5, 8). The pathogenic organism does not stain in tissue sections, although it
can be recovered by culture (5). F.
tularensis could not grow in our patients on standard culture media. Since
the culture and isolation of the bacterium is difficult, serologic tests are
performed for the diagnosis like our patients. The titer becomes positive 10-14
days after the onset of the disease. It is diagnostic for infection if a single
titre is > 160 or if there is a fourfold rise in the titer of antibody
to F. Tularensis. (5, 9)
Treatment
protocols appears to be based on case reports and anecdotal experience. The best
option in terms of efficacy and availability is IV gentamicin at 5 mg/kg twice
daily for 10 days. IV doxycycline, oral or IV ciprofloxacin have been described
as effective (1). Our patients were successfully treated with IV gentamicin
without complication or recurrence.
We
discuss the unique attributes of this disease along with appropriate steps that
lead to early identification of the
organism and effective treatment. Although isolation of infected patients is not
necessary and person-to-person spread has not been documented (1), another
aspect of this disease worth noting is that typhoidal or pneumonic tularemia,
especially in non-endemic areas, should suggest the possibility of an act of
bioterrorism.
Tularemia
should be considered in the differential diagnosis of cases with
non-tuberculosis, suppurative cervical lymphadenopathy, particularly in those
not responding to penicillin treatment, even in areas where it is not endemic.
Early diagnosis and treatment of tularemia are important to prevent abscess
formation, suppuration and healing with scar.
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