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\begin{document}

\title{Brucella pleurisy: An extremely rare complication of brucellosis}



\author[1]{Ahmad Alikhani}%
\author[1]{Hamideh Abbaspour Kasgari}%
\author[1]{Hadi Majidi}%
\author[1]{Zahra Nekoukar}%
\affil[1]{Mazandaran University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 28, 2024}


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\selectlanguage{english}
\begin{abstract}
Brucella, a zoonotic agent is a rare pathogen of the lung. This
intracellular organism can involve pleura in sub-acute and chronic
course of the disease, and it should be considered in endemic area of
brucellosis. Here, we present an extremely rare case of brucella
pleurisy that referred with chest pain.%
\end{abstract}%



\sloppy


\textbf{Introduction:}

Brucellosis is an endemic disease in many developing countries and is a
zoonotic infection of Brucella spp. mainly B. abortus and B.
melitensis.\textsuperscript{1} Contaminated dairy consumption or contact
with an infected animal is responsible for infecting
humans.\textsuperscript{2} The variability in clinical presentations,
including fluctuated fever, sweating, arthralgia, myalgia, back pain,
and hepatomegaly, is commonly implicated in the differential
diagnosis.\textsuperscript{3}

Cardiovascular, respiratory, and nervous system dysfunction, hepatitis,
and osteoarthritis are the most known complications of brucellosis.
Although Zheng et al. reported that the incidence of respiratory
involvement in brucellosis is about 13\%, which may represent cough,
pneumonia (or bronchial pneumonia), pleural effusion, pulmonary
embolism, or even respiratory failure, most previous studies announced
respiratory involvement as a rare complication.\textsuperscript{4} Here,
we present an extremely rare case of brucella pleurisy in a 40-year-old
man with low-grade fever, arthralgia, and chest pain.

\textbf{Case presentation:}

A 40-year-old smoker man, presented to our clinic with low grade fever,
arthralgia, and low back pain for several months. He was treating for
brucellosis (with doxycycline and rifampin) from 7 days before this
presentation, which was admitted for chest pain and dry cough. The lung
auscultation revealed decreased breathing sounds and dullness in
percussion in the base of right hemi-thorax. Cardiac examination was
normal and there was no lymphadenopathy or organomegaly. There was a
history of unpasteurized dairy product consumption and brucellosis in
his father several years ago.

Chest X-ray (CXR) showed blunting of the right costophrenic angle (CPA)
and in lung computed tomography (CT) scan, right pleural effusion
without significant parenchymal infiltration was seen. {[}\emph{Figure
1{]}}

Transthoracic echocardiography was normal. The level of the inflammatory
markers were high {[}C-reactive protein (CRP): 38 mg/L (0-1mg/L),
erythrocyte sedimentation rate (ESR): 115 mm/hr (\textless{}25
mm/hr){]}, and the platelet (PLT) count that was
502000/mm\textsuperscript{3}. Evaluation of rheumatologic markers were
negative (wright test and 2ME were 1/320 and 1/160, respectively).
{[}\emph{Table-1} {]} Pleural effusion aspirated and analyzed as we
showed the results in Table -2. The patient was treated for Brucella
pleurisy with gentamicin (240 mg/daily/IV) and ceftriaxone (1g every
12hr / IV) plus rifampin (600mg per day, orally) for 2 weeks. After 5
days, he had no fever, and after 7 days, his chest pain and cough
gradually decreased to disappear. Laboratory changes trend showed in
Table-1. Medications also changed to oral formulations after 2 weeks
with ofloxacin (300mg/daily) (intolerated to doxycycline) plus rifampin
for 10 weeks. The patient was followed on 6 and 12 weeks after discharge
and he did not have any complications and was improved completely. Lung
examination became normal and he was unsatisfied for repeating imaging.
Written informed consent was obtained from the patient for publication
of this report. This study was conducted according to the declaration of
Helsinki principles. Also, CARE guidelines and methodology were followed
in this study.

\textbf{Discussion:}

The diagnosis of brucellosis with a wide range of nonspecific clinical
presentations may last for months, as it occurred in our case, in which
the specific therapy was started for him after several months of being
symptomatic. The extended disease and inappropriate treatment may lead
to even more severe consequences and some of the body system
impairment.\textsuperscript{5} On the other hand, responding slowly to
the specific treatment is one of the characteristics of brucellosis, and
this feature led to pulmonary manifestations in our case while he had
been treated with effective medications for a week.

In addition to the common clinical findings in brucellosis, including
fever, headache, malaise and weakness, myalgia, arthralgia, backache,
and anorexia, some organs of the body may be affected like
gastrointestinal, respiratory, cardiovascular, hematopoietic, and
nervous systems.\textsuperscript{6}

Andriopoulos et al. in 2007 investigated the presentation, diagnosis,
and treatment of 144 cases of acute brucellosis. According to the data,
no one exerted respiratory impairment features; however, osteoarticular,
hematologic, or gastrointestinal complications were confirmed in many
cases.\textsuperscript{7}

The incidence of respiratory complications of brucellosis has been
reported lower than 1 to 5\%. The exact pathophysiology of this
complication is not defined well. The most reported symptoms are fever,
cough, dyspnea, sputum production, hemoptysis, and lymphadenopathy; and
the most radiographic findings are interstitial pattern, lobar
pneumonia, and pleural effusion.\textsuperscript{8}

Studies showed that timely diagnosis and appropriate treatment result in
a good prognosis. Hakan Erdem et al. in the largest series of pulmonary
brucellosis in 2014 showed that the most symptoms of the patients were
fatigue (87.2\%), cough (85.7\%), sweating (79.6\%), lack of appetite
(74.4\%), and arthralgia (68.4\%); while, our patient referred with
chest pain, arthralgia, and low-grade fever. In that research, the most
forms of pulmonary involvement were pneumonia, pleural effusion,
bronchitis, nodular lung lesions, pulmonary embolism, ARDS, and
surprisingly no pleurisy.\textsuperscript{9}

To the best of our knowledge, there are three published case reports of
brucella pleurisy, which all were completely recovered after treatment
with rifampin plus doxycycline for a total of 8 to 12 weeks. There were
also no radiological findings or relapses on their
follow-up.\textsuperscript{10-13} The same was happened to our case,
except for the selected regimen according to the patient's intolerance,
which was consisted of ofloxacin instead of doxycycline.

Brucellosis and tuberculosis (TB) often are endemic in some regions
simultaneously. Since they are completely different in treatment
strategies, it is important to differentiate the respiratory involvement
of brucellosis from TB infection.\textsuperscript{14} Of course, the
presence of arthralgia along with the history of unpasteurized dairy
products consumption can be considered to the detriment of TB diagnosis.
Since Iran is an endemic region for TB, TB infection was ruled out for
our patient with a negative MTB-PCR test. It should be noted that the
pleural fluid adenosine deaminase (ADA) levels elevate in TB, and
measuring ADA alone could not help to confirm
brucellosis.\textsuperscript{10}

\textbf{Conclusion:}

Brucella pleurisy is an extremely rare complication of brucellosis, even
in an endemic region. The physician should always be aware of any
symptom associated with respiratory involvement in a patient with
brucellosis or with a history of the disease, because this complication
may occur in the sub-acute phase of the disease. In the case of uncommon
brucella pleurisy, effective management can result in both clinical and
radiological improvement.

\textbf{Conflict of interest:}

Declared none.

\textbf{Authorship contribution:}

AA and HM involved in the interpretation and collecting of data and
editing of the manuscript. ZN and HAK involved in drafting the first
version of the manuscript. ZN involved in editing, and preparing the
final version of the manuscript. AA is involved in critically revising
the whole manuscript. All authors reviewed the paper and approved the
final version of the manuscript.

\textbf{Consent:}

Written informed consent was obtained from the patient for publication
of this report.

\textbf{Availability of data:}

Data sharing is not applicable to this article as no new data were
created or analyzed in this study.

Figure 1. Radiological findings showing pleurisy\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

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\end{figure}

\textbf{Table 1. laboratory data}\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
Parameters & Baseline values & 2 weeks after treatment & 8weeks after
treatment\tabularnewline
\midrule
\endhead
WBC Count (/ \selectlanguage{greek}μ\selectlanguage{english}L) & 20000 & 7200 & -\tabularnewline
PMN (\%) & 84.7 & 61.3 & -\tabularnewline
Lymph. (\%) & 6.5 & 31.2 & -\tabularnewline
Mono. (\%) & 5.4 & 4.8 & -\tabularnewline
Eos. (\%) & 3.4 & 2.7 & -\tabularnewline
Hb(g/dl) & 4.3 & 13.5 & -\tabularnewline
PLT (/ \selectlanguage{greek}μ\selectlanguage{english}L) & 502000 & 392000 & -\tabularnewline
ESR & 115 & 85 & -\tabularnewline
CRP & 38 & 20 & -\tabularnewline
Wright Test & 1/320 & - & 1/160\tabularnewline
2ME & 1/160 & - & 1/80\tabularnewline
Serum IDH & 246 & &\tabularnewline
Serum Protein & 3.2 & - & -\tabularnewline
Covid-19 PCR on Nasopharyngeal swab & Negative & Negative &
Negative\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2. Pleural Fluid Analysis}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Parameter & Results\tabularnewline
\midrule
\endhead
WBC (/ \selectlanguage{greek}μ\selectlanguage{english}L) & 300\tabularnewline
PMN (\%) & 30\%\tabularnewline
Lymph (\%) & 70\%\tabularnewline
RBC & 4000\tabularnewline
Glucose(mg/dl) & 68\tabularnewline
IDH(IU/L) & 17.0\tabularnewline
Protein(g/dl) & 2.7\tabularnewline
ADA(NL\textless{}30IU/L) & 16\tabularnewline
Wright Test Gram stain Bacteriologic culture Ziehl-Neelsen for AFB
Cytology for malignancy & 1/160 Negative No growth Negative
Negative\tabularnewline
Culture on Castaneda medium & No growth after 3 weeks\tabularnewline
MTB-PCR & Negative\tabularnewline
\bottomrule
\end{longtable}

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10. Dikensoy O, Namiduru M, Hocaoglu S, Ikidag B, Filiz A. Increased
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12. Karahocagil MK, Akdeniz H, Kirik\selectlanguage{ngerman}çi AD, Karsen H, Serto\selectlanguage{polish}ğ\selectlanguage{english}ullari B.
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13. Ulu\selectlanguage{polish}ğ \selectlanguage{english}M, Can-Ulu\selectlanguage{polish}ğ \selectlanguage{english}N. Pulmonary involvement in
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14. el Amrani A, AJ CT, Jim\selectlanguage{ngerman}énez-Alonso J. Simultaneous isolation of
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