despite the better control of tuberculosis ( tb ) in the world , the proportion of extrapulmonary tb has increased in recent years . in this context , peritoneal tb ( ptb ) represents the most frequent form of abdominal tb .
data are lacking in developed countries since most studies were done in endemic countries of tb [ 24 ] .
the aim of the present study was to describe the clinical presentation , diagnosis , bacterial epidemiology , treatment , and outcome of ptb in two university hospitals in france over a 10-year period .
all patients diagnosed with ptb in the university hospitals of lyon ( croix - rousse hospital ) and nancy ( brabois hospital ) between january 2004 and december 2014 were included in a retrospective observational study .
france is a country with an incidence of 8.7 per 100,000 population ( including 27% of extrapulmonary )   and the two cities lyon and nancy count 1.3  million and 300,000 people , respectively .
patients were identified by using the database of the administrative coding system ( patients with diagnosis of ptb in the infectious disease unit ) and the database of the mycobacteriological laboratory of lyon and nancy ( patients with a positive culture or polymerase chain reaction [ pcr ] of ascites or peritoneum ) .
patients without culture or pcr confirmation of tb but with peritonitis consistent with ptb based on clinical , radiographic or histologic evidence were included .
ascites samples were processed in biosafety level 3 facility as follows : briefly samples were centrifuged for 15  min before inoculation to solid ( lwenstein - jensen ) and liquid ( mgit - bactec ) media .
pellets were heat inactivated and then used for acid fast bacilli smear test with fluorescent microscope .
heat - inactivated samples were further processed for dna extraction with magna pure roche system and then used for mycobacterium  tuberculosis specific in house pcr reaction .
cultured strains were characterized by spoligotyping ( spacer oligonucleotide typing ) , a pcr - based method for genotyping strains   and categorized by lineage , using the spoldb4 database .
all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1964 , as revised in 2013 .
thirty - four patients were included ( 29 in lyon and 5 in nancy ) .
there was male predominance , with 22 men and 12 women ; median age was 40  years .
twenty - six patients ( 76.5% ) were migrants from areas of endemic tb , mainly africa .
one or more underlying disease was found in 13 patients ( 38.2% ) : liver cirrhosis ( 6 ) , diabetes mellitus ( 6 ) , chronic viral hepatitis ( 4 ) or immunodepression as cancer ( 4 ) , immunosuppressive therapy ( 3 ) and human immunodeficiency virus ( 1 , who was already treated and controlled ) .
two patients ( 5.9% ) had history of cured tb ; history of tb exposure was reported by seven patients ( 20.6% ) .
the main presentation that lead to hospitalization ( 29 patients : 85.3% ) was a checkup of ascites or suspicion of peritoneal carcinomatosis ; two patients ( 5.9% ) presented peritonitis . the main symptoms and signs are given in table  1 .
four patients ( 11.8% ) presented acute abdominal illness requiring emergency laparotomy ( two initially and two secondarily ) .
median symptom duration before admission was 1  month.table  1symptoms and signs at the presentation ( n  =  34)symptoms 
 n ( % ) fever and/or sweats24 ( 70.6%)abdominal pain24 ( 70.6%)ascites or abdominal swelling19 ( 55.9%)weight loss16 ( 47.1%)asthenia11 ( 32.4%)diarrhea4 ( 11.8%)anorexia3 ( 8.8%)abdominal mass1 ( 2.9%)salpingitis1 ( 2.9% ) symptoms and signs at the presentation ( n  =  34 ) biological findings revealed biological inflammatory syndrome in all patients , with a median c - reactive protein level of 95  mg / l . lymphopenia ( under 1.5 
g / l ) was found in 23 of the 30 patients investigated ( 76.7% ) .
interferon- release assay ( quantiferon - tb ; cellestis ) was positive in only 16/22 patients ( 72.7% ) , and 15/24 ( 62.5% ) had positive ( at least 10  mm ) tuberculin test ( tubertest ; sanofi pasteur ) .
ascitic fluid analysis found exudate in 17/21 patients ( 80.1% ) , with lymphocytic predominance in 19/21 cases ( 90.5% ) . on abdominal computed tomography ( ct )
, ascites was found in 29/32 patients ( 90.6% ) , and was the only abnormality in 4/32 of these ( 13.8% ) .
only three patients ( 8.9% ) had no ascites on ct scan , corresponding to the  dry plastic  form of ptb , defined by bhargava .
abdominal ultrasound was equal to ct to detect ascites ( 25/28 , 89.3% ) but less efficient in detecting peritoneal thickening ( 6/28 , 21.4% ) .
six patients ( 17.8% ) had positron emission tomography , showing increased peritoneal or mesenteric and lymph node metabolic activity , which could not be differentiated from carcinomatosis .
thirty - two out of 34 thoracic ct ( 94.1% ) were abnormal with pleural effusion ( 12 ) , mediastinal lymph node ( 9 ) , micronodules ( 8) , nodule ( 4 ) , or excavation ( 1 ) . surgery was required for diagnosis in 20 cases ( 58.8% ) , including 14 laparoscopies ( 41.2% ) and six laparotomies ( 17.6% ) .
intraoperative visual inspection was suggestive of ptb in 13 patients ( 65% ) , with typical small white peritoneal granulations or granuloma .
six of the patients who did not undergo surgery ( 42.9% ) had ultrasound - guided peritoneal biopsy .
diagnostic performance of the various bacteriological and histological analyses is shown in table  2 .
tb pcr , performed on 13/31 ascites samples and on 8/14 peritoneal biopsies , was systematically negative on ascites and positive on only 2 peritoneal biopsies ( 25% ) .
it should be noted that a large number of peritoneal biopsies were not sent to the bacteriology laboratory ( 8/22 , 36.4% ) , because only malignant ascites was suspected by the surgeon .
finally , histological and/or bacteriological diagnostic proof was obtained in all patients , except for three ( 8.8% ) who did not have peritoneal biopsy but were cured by the anti - tb treatment.fig . 
1abdominal computed tomography of a peritoneal tuberculosis , with peritoneal nodular thickening ( white arrow ) and ascitestable  2diagnostic performance of bacteriological and histological analyses in patients with peritoneal tuberculosisascitesperitoneal biopsytotal3222positive culture58.1% ( 18/31)71.4% ( 10/14)positive pcr0.0% ( 0/13)25.0% ( 2/8)total bacteriological performance58.1% ( 18/31)73.3% ( 11/15)histological performance : epithelioid giant - cell granuloma95.5% ( 21/22)including with caseous necrosis36.4% ( 8/22 ) 
 pcr polymerase chain reaction abdominal computed tomography of a peritoneal tuberculosis , with peritoneal nodular thickening ( white arrow ) and ascites diagnostic performance of bacteriological and histological analyses in patients with peritoneal tuberculosis 
 pcr polymerase chain reaction twenty - six infections were documented .
mycobacterium  bovis was isolated in 6 patients ( 23.1% ) and m.  tuberculosis in the others 20 ( 76.9% ) .
all isolates were susceptible to classical anti - mycobacterial drugs , except one case of isoniazid resistance ( m.  bovis is naturally resistant to pyrazinamide ) .
genetic analysis by spoligotyping , performed in 21 cases , revealed that 8 ( 38% ) belonged to lineage t ( table  3 ) .
t family lineage is characterized by the absence of spacers 3336 among the 43 spacers targeted by spoligotyping ; the prototypic shared spoligotype is sit53 .
there was no specific clinical characteristic for the spoligotype t.table  3spoligotyping of the 21 strains responsible for peritoneal tuberculosis spoligotyping of the 21 strains responsible for peritoneal tuberculosis sixteen patients ( 47.1% ) showed one or more other tb location , including lung ( five patients ) , and digestive ( four patients ) , gynecological ( four patients ) and urological ( two patients ) tract .
sputum smear examination or bronchoalveolar lavage was performed in 32 patients ( 94.1% ) and cultures were positive for 5 patients ( 14.7% ) .
extensive surgery with intestinal resection was required in two patients because of digestive perforation ; corticosteroids were prescribed for subocclusive syndrome in two patients ; and three malnourished patients required artificial nutrition .
antimycobacterial therapy comprised standard regimen with daily rifampicin , isoniazid , ethambutol and pyrazinamide during 2  months followed by at least 4 months of rifampicin and isoniazid for 24 patients ( 70.6% ) ; the others had therapy without pyrazinamide or without isoniazid and/or with quinolone because of toxicity or hepatic disorder before treatment .
side - effects led to dose decrease or a change of treatment in 13 patients ( 38.2% ) .
twenty - six patients ( 76.5% ) completed treatment and were clinically and radiologically cured ; four were lost to follow - up ; one was still under treatment at the time of writing ; and three died during treatment ( only one because of disseminated tb ) .
median treatment duration was 8.5  months , and follow - up without relapse after end of treatment was 12  months .
early diagnosis of ptb is a challenge as the main presentation of our cohort ( 85.3% ) was a checkup of ascites or suspicion of peritoneal carcinomatosis .
due to non - specific and insidious symptoms , there is a significant delay before diagnosis and treatment , even in developed countries .
notably , most cases of ptb mimic peritoneal carcinomatosis , especially in women with elevated blood ca 125 . in cirrhotic patients
bacteriological performance is imperfect since culture of ascites was positive in only 58.1% and peritoneal biopsy in 73.3% of cases .
histology allows to correct the diagnosis of tb in a large number of cases where bacterial culture was forgotten : it is essential to routinely do mycobacterial culture of peritoneal biopsy during an exploration of ascites or peritoneal thickening , unless there is a known intra - abdominal malignancy .
laparoscopic peritoneal biopsy is the reference method for diagnosis of ptb but , as described here , ultrasound - guided biopsy may facilitate diagnosis , with a lower risk of complications .
culture of ascites fluid must be systematic , even if the positivity rate is lower than for peritoneal biopsy , probably because of the low number of bacilli in the processed samples . in the present study , tb pcr seemed to be insensitive when performed on ascites , but can be useful on peritoneal biopsy .
interestingly , we found that a high percentage of isolates responsible for ptb belonged to lineage t. extrapulmonary tb is usually more frequently associated with the east african - indian or central - asian lineages , whereas lineage t , like the beijing lineage , seems to be more frequently linked to pulmonary forms [ 13 , 14 ] .
the t lineage is the predominant lineage in europe , but not in africa , where most of our patients have lived before migrating in france .
finally , it is not known if particular lineages are more frequently responsible for ptb and more data are required to directly incriminate the t lineage in the pathophysiology of ptb . in case of suspected ptb , especially with concordant histology
, physicians should not wait for culture before initiating treatment , since treatment delay is a very important factor of poor prognosis .
the present cure rate was high , and there was no relapse during follow - up .
ultrasound - guided peritoneal biopsy may facilitate diagnosis . tb pcr can be useful on peritoneal biopsy .
zo cavalli , florence ader , florent valour , julien saison , loc boussel , oana dumitrescu , thomas perpoint , christian chidiac , thierry may , and tristan ferry declare that they have no conflicts of interest .
all procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation ( institutional and national ) and with the helsinki declaration of 1964 , as revised in 2013 .
this article is distributed under the terms of the creative commons attribution - noncommercial 4.0 international license ( http://creativecommons.org/licenses/by-nc/4.0/ ) , which permits any noncommercial use , distribution , and reproduction in any medium , provided you give appropriate credit to the original author(s ) and the source , provide a link to the creative commons license , and indicate if changes were made .
 introductiondiagnosis of peritoneal tuberculosis ( ptb ) is difficult , even in developed countries , where data are lacking . 
 the aim of the present study was to describe the clinical presentation , diagnosis , and bacterial epidemiology of ptb in france over a 10-year period.methodsa retrospective study was conducted on ptb in two university hospitals in france , between january 2004 and december 2014.resultsamong the 34 patients , 76.5% were migrants from areas of endemic tuberculosis ( tb ) , mainly africa . the main presentation ( 85.3% ) was a checkup of ascites or suspicion of peritoneal carcinomatosis . on abdominal computed tomography , 
 ascites was found in 90.6% and peritoneal thickening in 75% . 
 surgery was required for diagnosis in 58.8% of patients . 
 six of the patients who did not undergo surgery had ultrasound - guided peritoneal biopsy . 
 bacteriology was positive for ascites in only 58.1% of cases , for peritoneal biopsy in 73.3% , while granuloma was found in 95.5% . 
 tb polymerase chain reaction ( pcr ) was positive in 25% of peritoneal biopsy . 
 mycobacterium bovis was isolated in 23.1% of cases and mycobacterium tuberculosis in 76.9% . 
 isolates were fully susceptible ( except m.  bovis naturally resistant to pyrazinamide ) . 
 many ( 38% ) belonged to the lineage t ( genetic analysis by spoligotyping ) . 
 cure rate was high ( 76.5% ) , after a 69  months of anti - tuberculous therapy.conclusionin developed countries , early diagnosis of ptb is still a challenge . 
 ultrasound - guided peritoneal biopsy may facilitate diagnosis . tb pcr can be useful on peritoneal biopsy . 
 the lineage t was the most prevalent lineage , but more data are required to directly incriminate this lineage in the pathophysiology of ptb . 
Introduction
Methods
Results
Discussion
Conclusions
Disclosures
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