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Travel Medicine and Infectious Disease (2014) 12, 667e672

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Brucellar epididymo-orchitis: A
retrospective multicenter study of 28 cases
and review of the literature
Umit Savasci a, Murat Zor b,*, Ahmet Karakas c, Emsal Aydin d,
Ramazan Kocaaslan e, N. Cem Oren f, Omer Coskun c,
Vedat Turhan g, H. Cem Gul c, A. Fuat Cicek h, Emin Aydur i,
Can Polat Eyigun c

a
Sarkams Military Hospital, Department of Infectious Diseases and Clinical Microbiology, Kars,
Turkey
b
Sarkams Military Hospital, Department of Urology, Kars, Turkey
c
Gulhane Military Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara,
Turkey
d
Kafkas Application and Research Hospital of Medicine Faculty, Department of Infectious Diseases and
Clinical Microbiology, Kars, Turkey
e
Kafkas Application and Research Hospital of Medicine Faculty, Department of Urology, Kars, Turkey
f
Sarkams Military Hospital, Department of Radiology, Kars, Turkey
g
GATA Haydarpasa Training Hospital, Department of Infectious Diseases and Clinical Microbiology,
Istanbul, Turkey
h
Gulhane Military Hospital, Department of Pathology, Ankara, Turkey
i
Gulhane Military Hospital, Department of Urology, Ankara, Turkey

Received 3 February 2014; received in revised form 3 August 2014; accepted 1 October 2014
Available online 25 October 2014

KEYWORDS Summary Objective: To review retrospectively the clinical symptoms, laboratory findings
Brucella; and treatment outcomes of patients with Brucellar epididymo-orchitis.
Epididymis; Material and method: Retrospective data of 28 patients with Brucellar epididymo-orchitis who
Testis; admitted to four medical centers between 2005 and 2013 were retrospectively reviewed. Pos-
Orchitis; itive blood culture, positive Rose Bengal test results or high agglutination titres of 1/160 with
Granulomatous the positive clinical and ultrasonographic findings of orchitis were accepted as the main
criteria for Brucellar epididymo-orchitis.
Results: The mean patient age was 31  16.9 years. Testicular involvement was on the left side
in 16 patients and on the right side in 11 patients, one had bilateral disease. Testicular pain

* Corresponding author. Department of Urology, Gulhane Military Medical Academy, School of Medicine, 06018 Ankara, Turkey. Tel.: 90
312 3045610; fax: 90 312 3042150.
E-mail address: murat804@yahoo.com (M. Zor).

http://dx.doi.org/10.1016/j.tmaid.2014.10.005
1477-8939/ 2014 Elsevier Ltd. All rights reserved.
668 U. Savasci et al.

and swelling were the most common symptoms and elevation of C-reactive protein (CRP),
erythrocyte sedimentation rate (ESR) and leucocytosis were the most common laboratory find-
ings. Initial treatment was orchidectomy in six patients due to malignancy suspicion. All but
three patients were successfully treated with antibiotic combinations of rifampicin, doxycy-
cline and streptomycin. Two of three treatment resistant patients underwent orchidectomy.
Conclusion: Brucellosis is a common cause of epididymo-orchitis in endemic regions. Early
diagnosis and treatment is crucial in the management and thus it must be kept in mind in
endemic and non-endemic regions.
2014 Elsevier Ltd. All rights reserved.

1. Introduction criteria for orchitis. Scrotal ultrasonography was also used


to determine if there was an additional complication such
Brucellosis is an endemic zoonotic disease caused by as abscess formation. Blood samples were taken from pa-
Brucellosis spp., gram negative coco-bacilli [1]. It is hy- tients with fewer.
perendemic in Arabian peninsula, Mediterranean region,
India, Central and South America. In Turkey central, 3. Results
eastern and south eastern regions are more affected [2].
Brucella is transmitted through the direct contact with A total of 28 patients with BEO during 8 years period were
infected tissues or through gastrointestinal tract after analyzed. The mean patient age was 31  16.9 (8e79)
consumption of the contaminated products. It also can be years. Most of the patients were in their late 20s (33%).
transmitted through respiratory system after inhalation and Epididymo-orchitis was unilateral in all cases except a 9
through the conjunctiva [3]. year old child. Of these 27 unilateral epididymo-orchitis
Human brucellosis is a multisystemic disease with a wide patients left and right testicle involvement was seen in 16
clinical spectrum. Undifferentiated febrile disease, and 11 patients, respectively. However, testicular pain and
arthritis with hepatosplenomegaly and lymphadenopathy swelling were the most common symptoms, sweating,
are the usual presentation types, however, the symptoms fever, chilling, fatigue, dysuria and anorexia were also
are usually nonspecific. Focal complications and single commonly seen (Table 1). Cutaneous fistulisation were seen
organ involvement can involve almost all organ systems and in two patients. Arthralgia was seen in one and hep-
can occur 20e40% of cases [4]. While genitourinary system atosplenomegaly was seen in four patients.
involvement is the second most common complication after Rose Bengal test positivity was seen in all patients.
locomotor system involvement, epididymo-orchitis is the Serum tube agglutination was performed 14 of 28 patients
most frequent type of genitourinary complication and af- and high titres of 1/160 were detected in 11 of 14 patients
fects 2e20% of men [5]. It causes a granulomatous type of (78.5%). Blood cultures were sampled in 9 patients with
orchitis [6]. fewer and of these 5 were positive for Brucella species. On
In this retrospective multicenter study, we analyzed the other hand the most common laboratory finding was the
epidemiologic, clinical, laboratory data and the treatment elevation of C-reactive protein (CRP). The following
and outcome characteristics of 26 cases with brucellar
epididymo-orchitis (BEO).

Table 1 Clinical symptoms of the patients with brucellar


2. Material and methods epididymo-orchitis.
Symptoms No. (%)
The retrospective study was conducted after approval by
the local committee of our Medical Academy. From 2005 to Testicular pain and swelling 28 (100)
2013, data of 28 patients with BEO who admitted to four Sweating 10 (36)
medical centers (urology and infectious diseases and clin- Fewer 9 (32)
ical microbiology departments) were retrospectively Scrotal redness 7 (25)
reviewed. Blood culture, standard tube agglutination Chilling 8 (29)
testing and Rose Bengal test were used as diagnostic tools. Fatigue 8 (29)
Positive blood culture, positive Rose Bengal test results or Dysuria 8 (29)
high agglutination titres of 1/160 with the positive clinical Anorexia 8 (29)
(e.g. fewer, testicular pain or tenderness and scrotal Weight loss 1 (3)
swelling) and ultrasonographic findings of orchitis were Vomiting 1 (3)
accepted as the main criteria for BEO diagnosis. Testicular Cutaneous fistulisation 2 (7)
enlargement, non-homogenous echotexture, hypoechoic or Hepatosplenomegaly 4 (14)
heterogeneous echogenecity and testicular hyper- Arthralgia 1 (3)
vascularity on Doppler are determined as the sonographic Note. Some patients had >1 signs and symptoms.
Brucellar epididymo-orchitis 669

common laboratory findings were elevated erythrocyte almost every system can be affected, however locomotor,
sedimentation rates (ESR) and leucocytosis. Anemia and gastrointestinal, urogenital, hematologic, cardiovascular,
thrombocytopenia were seen in one and two patients, respiratory and central nervous systems are the mostly
respectively. There was no report of high alkaline phos- infected sites [5]. BEO is a common clinical complication
phatase levels (Table 2). rather than a clinical finding of brucellosis and in several
Of total 28 patients 6 (21.4%) were pre-diagnosed as studies the incidence is reported to be 2e20% [7,8]. On the
testicular malignity and underwent radical orchidectomy. other hand 10e20% of epididymo-orchitis are estimated to
Testicular mass and swelling were predominant symptoms. be caused by Brucella species [9,10]. The diagnosis can be
Histopathologic examination of these patients revealed done by serologic tests, ultrasonographic findings in the
granulomatous inflammation (Fig. 1a) and following labo- presence of orchitis symptoms such as testicular pain,
ratory studies confirmed brucellosis. Adjuvant antibiotic swelling and redness, fewer and sweating. However,
treatment with rifampicin (1  600 mg/day) and doxycy- epididymo-orchitis is rarely the leading finding in most of
cline (2  100 mg/day) for 6 weeks were applied to all the cases and usually presents with typical findings of
these patients to treat the systemic disease and laboratory brucellosis, differential diagnosis from other causes of
and clinical cures were achieved. In the other 22 (78.6%) testicular mass formations and acute or chronic infections
patients the pre-diagnosis were BEO and except three cases especially tuberculosis is important in areas where the
all were successfully treated with 4 different antibiotic disease is endemic [11]. In our cases, 6 of 28 patients
treatment regimens (Table 3). In one patient treatment was (21.4%) were misdiagnosed and underwent orchidectomy.
extended to 12 weeks due to partial response to rifampicin The predominant symptom was diffuse testicular swelling
(1  600 mg/day) and doxycycline (2  100 mg/day) in three, focal testicular mass in two and testicular mass
treatment. In two patients no response were seen with and cutaneous fistulisation in one patient. It is reported in
rifampicin (1  600 mg/day) and doxycycline (2  100 mg/ the literature that, orchidectomy or inguinal exploration
day) treatment and cutaneous fistulisation occurred as a can be performed to the patients who have focal hypo-
long late complication of the disease (Fig. 1b). Not sur- echoic lesions in the testis seen on ultrasonography
prisingly the initial ultrasonographic evaluation of these [12e14]. As in our cases, in the absence of classical triad of
cases revealed abscess formation (Fig. 1c). Both cases were infection patients can be misdiagnosed and this can lead
finally successfully treated with orchidectomy. Histopath- overtreatment such as orchidectomy. In our opinion, it
ologic examination revealed necrotizing granulomatous must be kept in mind even in the patients who do not have
inflammation. In general, medical treatment response rate any symptoms of local or systemic infection.
was 86.3% in the patients with correct pre-diagnosis. BEO occurs mostly in young males. Similar to the pub-
lished previous literature [5,16], mean age of our patient
4. Discussion population was 31 years and most of them were in the
second and third decade of their life. The most common
presenting symptoms of disease are reported to be testic-
Brucellosis is still a worldwide public health problem, and
ular pain and swelling, fewer, scrotal redness and sweating
needs to be discussed as a cause of morbidity where is
[4,5,15]. Arthralgia and arthritis, chilling, hep-
endemic such as Mediterranean basin, the Middle East,
atosplenomegaly, myalgia, nausea, vomiting constitutional
India and Central and South America. It is a zoonotic in-
and dermatological findings can accompany to these com-
fectious disease which causes both systemic and specific
mon predominant symptoms. Testicular pain and swelling
organ involvement. Organ infections can be described as
were the most common symptoms in our case series and
focal infection or focal complication. In focal disease
seen in all cases. Fewer, sweating, scrotal redness, fatigue
and anorexia were the other common symptoms. Urinary
tract symptoms were not frequent and dysuria was found in
Table 2 Laboratory findings of the patients with brucellar 8 patients (28.5%) of all. Urine analysis was normal in most
epididymo-orchitis. of the patients in keeping with previous published reports
Laboratory findings No./total no. (%) [7,15].
CRP >5 mg/dl 20/22 (91) Laboratory and radiologic evaluation is also important in
ESR >20 mm/h 19/22 (86) diagnosis and differential diagnosis of BEO. Nonspecific
Leucocytosis 18/28 (64) laboratory findings such as CRP and ESR elevation, AST and
ALT >40 IU/I 14/28 (50) ALT increases, leucocytosis, anemia, and thrombocyto-
AST >40 IU/I 11/28 (39) penia should be documented [6,7,15e17]. Increases in CRP
Thrombocytopenia 2/28 (7) and ESR levels were the most common laboratory findings in
Anemia 1/28 (3) our patients. When we exclude six cases without symptoms
ALP >150 e e of acute infection and whose prior diagnosis was testicular
Rose Bengal positivity 28/28 (100) malignancy, more than 85% of cases showed CRP and ESR
Positive wright 11/14 (79) level increases. Although, Khan and Afsar et al. reported
agglutination (1/160) high incidences of leucocytosis [6,18], this has generally not
Positive blood culture 5/9 (56) been reported as being a typical feature of brucellosis
[19,20]. In our study the leucocytosis was detected in 18 of
CRP. C-reactive protein, ESR. erythrocyte sedimentation rate, 28 patients (64.2%). In contrast to previous reports a high
ALT. alanine transaminase, AST. aspartate transaminase, ALP.
incidence of leucocytosis and increased ESR and CRP levels
alkaline phosphatase.
were observed in our case series. This may be due to acute
670 U. Savasci et al.

Fig. 1 a. Granulomatous formation with caseating necrosis surrounded with epithelioid hystiocytes and lymphocytes (arrow
heads) can be seen on the left upper segment of the figure. In the right lower segment normal seminiferous tubules (arrows) are
observed which are separated from the upper granulomatous formation with a fibrous band (20 magnification H&E). b. Cutaneous
fistulisation in the right testis can be seen. c. A large fluid collection (abscess formation) with some peripheral testicular tissue
remnants on left testicle (white arrow) secondary to necrosis were seen on ultrasonography.

onset of BEO in our patients. Serum tube agglutination ti- orchitis in the former six patients and necrotizing granulo-
tres of 1/160 were noted in 11 of 14 patients and Rose matous orchitis in the latter two. In the other six patient,
Bengal test positivity was seen in the whole case group. ultrasonography confirmed epididymo-orchitis.
Previous studies reported blood culture positivity as Rapid diagnosis and correct medical treatment is crucial
14e69% and our population revealed 55% (5 of 9 patients) in the prognosis of BEO. Delayed diagnosis, insufficient
positive blood culture results [15,21]. Additionally positive treatment, and failure of patients to take prescribed drugs
culture results from epididymal aspirate, scrotal tissue and and very rarely antibiotic-resistant Brucella strains lead to
sperm was reported in the literature but these samples complications such as abscess formation, which may
were not collected from our patients [7,15]. require orchidectomy [15,19], and the institution of proper
In addition to clinical symptoms, physical examination antibiotic combinations with longer courses is crucial in the
and laboratory findings, scrotal ultrasonography and treatment of BEO [23,24]. The World Health Organisation
testicular scintigraphy can be used to assist diagnosis and (WHO) recommends 45 day course of doxycycline
differential diagnosis [22]. The findings of ultrasonography (2  100 mg/day, PO) and 15 day course of streptomycin
(testicular enlargement, inhomogeneous echotexture, (1  1 g/day, IM) treatment. Alternatively 45 day course of
hypoechoic or heterogenous echogenecity and testicular rifampicin (1X600-900 mg/day, PO) and doxycycline
hypervascularity on Doppler) are depends on inflammation (2  100 mg/day, PO) is also recommended [24]. The
so they are all nonspecific and can be detected in all eti- Ioannina recommendations, a recent consensus recom-
ologies of orchitis. Thus, these investigations are more mendation of an expert panel, also proposed doxycycline-
useful for investigating BEO complications and differential streptomycin and doxycycline-rifampicin as first line regi-
diagnosis rather than BEO diagnosis [15]. In our study pop- mens without quantifying the differences between them
ulation, ultrasonography ultrasonography raised the suspi- [25]. On the other hand, alternative treatments including
cion of malignancy and abscess formation in 6 and 2 some other antibiotics, such as fluoroquinolones and co-
patients, respectively. All underwent orchidectomy and trimoxazole and their combinations with rifampicin, and
Histopathologic examination revealed granulomatous also triple drug regimens are still being investigated. In

Table 3 Treatment approaches and antibiotic protocols of the cases.


Initial treatment No. (%) Secondary No.
treatment
6 weeks course of rifampicin 1  600 mg/day doxycycline 18 (64) *Orchidectomy 2
2  100 mg/day **Additional 6 weeks course 1
of rifampicin 1  600 mg/day doxycycline
2  100 mg/day
3 weeks course of streptomycine 1 mg/day 6 weeks 2 (7) e
course of doxycycline 2  100 mg/day
15 day course of ceftriaxone 2  1 gr metronidazole 1 (3) e
2  500 mg
Orchidectomy 7 (25) ***6 weeks course of rifampicin 7
1  600 mg/day doxycycline
2  100 mg/day
*Cutaneous fistulisation occurred during antibiotherapy.
**Treatment was extended to 12 weeks due to partial response.
***Pre-diagnosis was testicular malignity so adjuvant antibiotherapy needed.
Brucellar epididymo-orchitis 671

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