- Email: [email protected]
Hepato-peritoneal tuberculosis with negative interferon gamma assay (Quantiferon™) in an immunocompetent patient: A case report
+Model
ARTICLE IN PRESS
CLINRE-833; No. of Pages 2
Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxx.e1—xxx.e2
Available online at
ScienceDirect www.sciencedirect.com
LETTER TO THE EDITOR Hepato-peritoneal tuberculosis with negative interferon gamma assay (QuantiferonTM ) in an immunocompetent patient: A case report Introduction We report a case of associated hepatic and peritoneal tuberculosis with negative QuantiferonTM assay in an immunocompetent patient.
Case report A 41-years-old Comorian man was admitted to our department after presenting with a one-month history of abdominal pain and altered general condition. He had no personal or familial past and took no treatment. He was neither smoker nor alcohol consumer. He had been previously vaccinated against tuberculosis (BCG) and denied any recent travel or contact with the infected patients. He described a three-month history of progressive weakness, anorexia and weight loss of 5 kilograms in the last month. He complained of diffuse abdominal pain and night sweats. On arrival, the patient was hemodynamically stable and body temperature was 39.5 ◦ C. Physical examination revealed a tense abdomen with shifting dullness. There was no jaundice, no hepatomegaly and no splenomegaly. Bowel sounds were present. Furthermore, no peripheral lymph node was palpable and there was no peripheral edema. Heart sounds were normal with decreased breath sounds on the left lower chest. The rest of the physical examination was normal. The full blood count (FBC) and C-reactive protein (CRP) were normal. The biochemistry revealed isolated hyponatremia (129 mmol/L). Renal and liver function tests were normal. INR was 1.3 due to vitamin K dependent factors deficiency. Furthermore, levels of lactate dehydrogenase and beta-2-microglobulin were increased at 791 IU/L and 4 mg/L, respectively.
Urine cultures were sterile. HIV, HBV and HCV serologies were negative. Immunoglobulin levels (IgG, IgM and IgA) were normal. Three blood cultures were sterile and research of BK in sputum and three days gastric aspirations were negative. Adenosine deaminase assay (Diazyme-CobasTM 5000) was raised in blood (1.5N). QuantiferonTM assay was twice negative in serum. The ascitic tap found a lymphocytic exsudate (protein level = 59 g/L) with 1070 elements/mm3 (75% lymphocytes). Adenosine deaminase assay was raised in ascites (3.5N). Abdominal and pelvic CT confirmed the presence of intraperitoneal fluid and a left pleural effusion. Laparoscopy confirmed lymphocytic ascites with diffuse peritoneal and liver granulations. Peritoneal and hepatic biopsies both confirmed the presence of epithelioid granuloma with central caseous necrosis. Furthermore, Mycobacterium tuberculosis cultures were positive with the presence of mycobacterium tuberculosis antigen (SD TB ag MPT64 Rapid technic) despite negative DNA research (GeneXpert MIB/RIF-Cepheid) in peritoneal fluid. Presumptive antituberculosis treatment was introduced (rifampicin 10 mg/kg/d, isoniazid 5 mg/kg/d, pyrazinamide 40 mg/kg/d and ethambutol 30 mg/kg/d) and continued for 6 months after tuberculosis confirmation. There was dramatic evidence of favorable clinical evolution during treatment (ascites control, weight gain, transaminases normalization). Finally, peritoneal and hepatic tuberculosis with a negative QuantiferonTM assay diagnosis was made.
Discussion Peritoneal Tb is one of the most common localizations for extra-pulmonary Tb and mortality rate could reach up to 50% even treated [1]. Diagnosis of peritoneal Tb is suggested by findings at laparoscopy or laparotomy. Examination of peritoneal fluid is an extremely useful tool, confirming the presence of exsudative ascites consisting predominantly of lymphocytes (> 70%) as in our case [2]. In low-incomes countries, QuantiferonTM and adenosine deaminase (in blood and ascites) have become the main diagnostic tools for peritoneal and extra-pulmonary Tb in general. This is mainly due to the high costs or unavailability
http://dx.doi.org/10.1016/j.clinre.2015.11.006 2210-7401/© 2016 Published by Elsevier Masson SAS.
Please cite this article in press as: Bourgain G, et al. Hepato-peritoneal tuberculosis with negative interferon gamma assay (QuantiferonTM ) in an immunocompetent patient: A case report. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.11.006
+Model CLINRE-833; No. of Pages 2
ARTICLE IN PRESS
xxx.e2 of laparoscopic interventions and histological analysis. Nonetheless, adenosine deaminase in ascites (optimal cutoff value 30 to 37 IU/L) has a very high sensitivity at 94—97% and a specificity of 94% [3,4]. Similarly, QuantiferonTM assays in blood (optimal cut-off value 112 pg/mL) yielded a sensitivity of 92.9% and a specificity of 98—100% in Egypt, India and South Africa [4—6]. As a matter of fact, its high negative predictive value could avoid treating 50% of patients, even those with a positive tuberculin skin test [7]. IFN gamma assay can be negative in immunocompromised patients (i.e. AIDS) with peritoneal tuberculosis [8]. Our patient presented no signs or history suggestive of immunocompromised status (no neutropenia, normal lymphocytes blood count, negative HIV serology, and normal immunoglobulin M, G, A levels). Due to a high index of suspicion, presumptive classical antituberculosis quadritherapy (rifampicin, isoniazid, pyrazinamide and ethambutol) was introduced as recommended in case of absence of laparoscopy or awaiting peritoneal histological analysis and mycobacterium cultures. Response to anti-mycobacterium treatment is a strong positive retrospective tool to assess and confirm the diagnosis of Tb in absence of investigational proof, especially in endemic countries. This was evident in our patient, who showed signs of recovery only days after treatment introduction: fever and ascites regression, weight gain, and INR normalization within three months. Although no consensual treatment duration currently exists, a 6-month period of antituberculosis therapy has been proven to have the same efficacy and cure rate as a 9-month period of therapy [9].
Conclusion Laparoscopy is the main diagnostic tool in peritoneal tuberculosis confirmed by bacteriological and pathological analyses (positive culture positive for M. tuberculosis in ascitic fluid granulomatous with caseous necrosis in liver tissue and peritoneum in our case) [10]. Even if recommended in endemic countries in absence of laparoscopy and despite its high diagnostic value and high negative predictive value, IFN gamma assay (QuantiferonTM ) can be deceivingly negative in documented peritoneal tuberculosis even in an immunocompetent patient as shown in this observation. In low-income countries, clinical response to presumptive antituberculosis treatment may be considered of major diagnostic value in patients with high suspicion of Tb and a negative QuantiferonTM assay.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Chow KM, Chow VCY, Hung LCT, Wong SM, Szeto CC. Tuberculous peritonitis-associated mortality is high among patients
Letter to the editor
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
waiting for the results of mycobacterial cultures of ascitic fluid samples. Clin Infect Dis 2002;35:409—13. Abdelaal A, Alfkey R, Abdelaziem S, Abunada M, Alfaky A, Ibrahim WH, et al. Role of laparoscopic peritoneal biopsy in the diagnosis of peritoneal tuberculosis. A seven-year experience. Chirurgia (Bucur) 2014;109:330—4. Tao L, Ning HJ, Nie HM, Guo XY, Qin SY, Jiang HX. Diagnostic value of adenosine deaminase in ascites for tuberculosis ascites: a meta-analysis. Diagn Microbiol Infect Dis 2014; 79:102—7. Sharma SK, Tahir M, Mohan A, Smith-Rohrberg D, Mishra HK, Pandey RM. Diagnostic accuracy of ascitic fluid IFN gamma and adenosine deaminase assays in the diagnosis of tuberculous ascites. J Interferon Cytokine Res 2006;26:484—8. Saleh MA, Hammad E, Ramadan MM, Abd El-Rahman A, Enein AF. Use of adenosine deaminase measurements and QuantiferonTM in the rapid diagnosis of tuberculous peritonitis. J Med Microbiol 2012;61:514—9. Sathar MA, Simjee AE, Coovadia YM, Soni PN, Moola SA, Insam B, et al. Ascitic fluid gamma interferon concentrations and adenosine deaminase activity in tuberculous peritonitis. Gut 1995;36:419—21. Su SB, Qin SY, Guo XY, Luo W, Jiang HX. Assessment by metaanalysis of interferon gamma for the diagnosis of tuberculous peritonitis. World J Gastroenterol 2013;19:1645—51. Schichter-Konfino V, Halasz K, Grushko G, Snir A, Haj T, Vadasz Z, et al. Interferon gamma release assay prevents unnecessary tuberculosis therapy. Isr Med Assoc J 2015;17:223—6. Makharia GK, Ghoshal UC, Ramakrishna BS, Agnihotri A, Ahuja V, Chowdhury SD, et al. Intermittent directly observed therapy for abdominal tuberculosis: a multicenter randomized controlled trial comparing 6 months versus 9 months of therapy. Clin Infect Dis 2015;61:750—7. Burke KA, Patel A, Jayaratnam A, Thiruppathy K, Snooks SJ. Diagnosing abdominal tuberculosis in the acute abdomen. Int J Surg 2014;12:494—9.
G. Bourgain a W. Sbai a L. Luciano a M.P. Massoure a S. Brardjanian a G. Goin b C. De Biasi c A. Wolf d A. Al Shukry e T. Coton a,∗ a Service de pathologie digestive, hôpital d’instruction des armées Laveran, CS 50004, 13384 Marseille cedex 13, France b Service de chirurgie viscérale, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France c Laboratoire d’anatomo-pathologie, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France d Laboratoire de biologie, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France e Service d’ORL, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France ∗
Corresponding author. E-mail address: [email protected] (T. Coton)
Please cite this article in press as: Bourgain G, et al. Hepato-peritoneal tuberculosis with negative interferon gamma assay (QuantiferonTM ) in an immunocompetent patient: A case report. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.11.006
ARTICLE IN PRESS
CLINRE-833; No. of Pages 2
Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxx.e1—xxx.e2
Available online at
ScienceDirect www.sciencedirect.com
LETTER TO THE EDITOR Hepato-peritoneal tuberculosis with negative interferon gamma assay (QuantiferonTM ) in an immunocompetent patient: A case report Introduction We report a case of associated hepatic and peritoneal tuberculosis with negative QuantiferonTM assay in an immunocompetent patient.
Case report A 41-years-old Comorian man was admitted to our department after presenting with a one-month history of abdominal pain and altered general condition. He had no personal or familial past and took no treatment. He was neither smoker nor alcohol consumer. He had been previously vaccinated against tuberculosis (BCG) and denied any recent travel or contact with the infected patients. He described a three-month history of progressive weakness, anorexia and weight loss of 5 kilograms in the last month. He complained of diffuse abdominal pain and night sweats. On arrival, the patient was hemodynamically stable and body temperature was 39.5 ◦ C. Physical examination revealed a tense abdomen with shifting dullness. There was no jaundice, no hepatomegaly and no splenomegaly. Bowel sounds were present. Furthermore, no peripheral lymph node was palpable and there was no peripheral edema. Heart sounds were normal with decreased breath sounds on the left lower chest. The rest of the physical examination was normal. The full blood count (FBC) and C-reactive protein (CRP) were normal. The biochemistry revealed isolated hyponatremia (129 mmol/L). Renal and liver function tests were normal. INR was 1.3 due to vitamin K dependent factors deficiency. Furthermore, levels of lactate dehydrogenase and beta-2-microglobulin were increased at 791 IU/L and 4 mg/L, respectively.
Urine cultures were sterile. HIV, HBV and HCV serologies were negative. Immunoglobulin levels (IgG, IgM and IgA) were normal. Three blood cultures were sterile and research of BK in sputum and three days gastric aspirations were negative. Adenosine deaminase assay (Diazyme-CobasTM 5000) was raised in blood (1.5N). QuantiferonTM assay was twice negative in serum. The ascitic tap found a lymphocytic exsudate (protein level = 59 g/L) with 1070 elements/mm3 (75% lymphocytes). Adenosine deaminase assay was raised in ascites (3.5N). Abdominal and pelvic CT confirmed the presence of intraperitoneal fluid and a left pleural effusion. Laparoscopy confirmed lymphocytic ascites with diffuse peritoneal and liver granulations. Peritoneal and hepatic biopsies both confirmed the presence of epithelioid granuloma with central caseous necrosis. Furthermore, Mycobacterium tuberculosis cultures were positive with the presence of mycobacterium tuberculosis antigen (SD TB ag MPT64 Rapid technic) despite negative DNA research (GeneXpert MIB/RIF-Cepheid) in peritoneal fluid. Presumptive antituberculosis treatment was introduced (rifampicin 10 mg/kg/d, isoniazid 5 mg/kg/d, pyrazinamide 40 mg/kg/d and ethambutol 30 mg/kg/d) and continued for 6 months after tuberculosis confirmation. There was dramatic evidence of favorable clinical evolution during treatment (ascites control, weight gain, transaminases normalization). Finally, peritoneal and hepatic tuberculosis with a negative QuantiferonTM assay diagnosis was made.
Discussion Peritoneal Tb is one of the most common localizations for extra-pulmonary Tb and mortality rate could reach up to 50% even treated [1]. Diagnosis of peritoneal Tb is suggested by findings at laparoscopy or laparotomy. Examination of peritoneal fluid is an extremely useful tool, confirming the presence of exsudative ascites consisting predominantly of lymphocytes (> 70%) as in our case [2]. In low-incomes countries, QuantiferonTM and adenosine deaminase (in blood and ascites) have become the main diagnostic tools for peritoneal and extra-pulmonary Tb in general. This is mainly due to the high costs or unavailability
http://dx.doi.org/10.1016/j.clinre.2015.11.006 2210-7401/© 2016 Published by Elsevier Masson SAS.
Please cite this article in press as: Bourgain G, et al. Hepato-peritoneal tuberculosis with negative interferon gamma assay (QuantiferonTM ) in an immunocompetent patient: A case report. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.11.006
+Model CLINRE-833; No. of Pages 2
ARTICLE IN PRESS
xxx.e2 of laparoscopic interventions and histological analysis. Nonetheless, adenosine deaminase in ascites (optimal cutoff value 30 to 37 IU/L) has a very high sensitivity at 94—97% and a specificity of 94% [3,4]. Similarly, QuantiferonTM assays in blood (optimal cut-off value 112 pg/mL) yielded a sensitivity of 92.9% and a specificity of 98—100% in Egypt, India and South Africa [4—6]. As a matter of fact, its high negative predictive value could avoid treating 50% of patients, even those with a positive tuberculin skin test [7]. IFN gamma assay can be negative in immunocompromised patients (i.e. AIDS) with peritoneal tuberculosis [8]. Our patient presented no signs or history suggestive of immunocompromised status (no neutropenia, normal lymphocytes blood count, negative HIV serology, and normal immunoglobulin M, G, A levels). Due to a high index of suspicion, presumptive classical antituberculosis quadritherapy (rifampicin, isoniazid, pyrazinamide and ethambutol) was introduced as recommended in case of absence of laparoscopy or awaiting peritoneal histological analysis and mycobacterium cultures. Response to anti-mycobacterium treatment is a strong positive retrospective tool to assess and confirm the diagnosis of Tb in absence of investigational proof, especially in endemic countries. This was evident in our patient, who showed signs of recovery only days after treatment introduction: fever and ascites regression, weight gain, and INR normalization within three months. Although no consensual treatment duration currently exists, a 6-month period of antituberculosis therapy has been proven to have the same efficacy and cure rate as a 9-month period of therapy [9].
Conclusion Laparoscopy is the main diagnostic tool in peritoneal tuberculosis confirmed by bacteriological and pathological analyses (positive culture positive for M. tuberculosis in ascitic fluid granulomatous with caseous necrosis in liver tissue and peritoneum in our case) [10]. Even if recommended in endemic countries in absence of laparoscopy and despite its high diagnostic value and high negative predictive value, IFN gamma assay (QuantiferonTM ) can be deceivingly negative in documented peritoneal tuberculosis even in an immunocompetent patient as shown in this observation. In low-income countries, clinical response to presumptive antituberculosis treatment may be considered of major diagnostic value in patients with high suspicion of Tb and a negative QuantiferonTM assay.
Disclosure of interest The authors declare that they have no competing interest.
References [1] Chow KM, Chow VCY, Hung LCT, Wong SM, Szeto CC. Tuberculous peritonitis-associated mortality is high among patients
Letter to the editor
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
waiting for the results of mycobacterial cultures of ascitic fluid samples. Clin Infect Dis 2002;35:409—13. Abdelaal A, Alfkey R, Abdelaziem S, Abunada M, Alfaky A, Ibrahim WH, et al. Role of laparoscopic peritoneal biopsy in the diagnosis of peritoneal tuberculosis. A seven-year experience. Chirurgia (Bucur) 2014;109:330—4. Tao L, Ning HJ, Nie HM, Guo XY, Qin SY, Jiang HX. Diagnostic value of adenosine deaminase in ascites for tuberculosis ascites: a meta-analysis. Diagn Microbiol Infect Dis 2014; 79:102—7. Sharma SK, Tahir M, Mohan A, Smith-Rohrberg D, Mishra HK, Pandey RM. Diagnostic accuracy of ascitic fluid IFN gamma and adenosine deaminase assays in the diagnosis of tuberculous ascites. J Interferon Cytokine Res 2006;26:484—8. Saleh MA, Hammad E, Ramadan MM, Abd El-Rahman A, Enein AF. Use of adenosine deaminase measurements and QuantiferonTM in the rapid diagnosis of tuberculous peritonitis. J Med Microbiol 2012;61:514—9. Sathar MA, Simjee AE, Coovadia YM, Soni PN, Moola SA, Insam B, et al. Ascitic fluid gamma interferon concentrations and adenosine deaminase activity in tuberculous peritonitis. Gut 1995;36:419—21. Su SB, Qin SY, Guo XY, Luo W, Jiang HX. Assessment by metaanalysis of interferon gamma for the diagnosis of tuberculous peritonitis. World J Gastroenterol 2013;19:1645—51. Schichter-Konfino V, Halasz K, Grushko G, Snir A, Haj T, Vadasz Z, et al. Interferon gamma release assay prevents unnecessary tuberculosis therapy. Isr Med Assoc J 2015;17:223—6. Makharia GK, Ghoshal UC, Ramakrishna BS, Agnihotri A, Ahuja V, Chowdhury SD, et al. Intermittent directly observed therapy for abdominal tuberculosis: a multicenter randomized controlled trial comparing 6 months versus 9 months of therapy. Clin Infect Dis 2015;61:750—7. Burke KA, Patel A, Jayaratnam A, Thiruppathy K, Snooks SJ. Diagnosing abdominal tuberculosis in the acute abdomen. Int J Surg 2014;12:494—9.
G. Bourgain a W. Sbai a L. Luciano a M.P. Massoure a S. Brardjanian a G. Goin b C. De Biasi c A. Wolf d A. Al Shukry e T. Coton a,∗ a Service de pathologie digestive, hôpital d’instruction des armées Laveran, CS 50004, 13384 Marseille cedex 13, France b Service de chirurgie viscérale, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France c Laboratoire d’anatomo-pathologie, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France d Laboratoire de biologie, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France e Service d’ORL, hôpital d’instruction des armées, CS 50004, 13384 Marseille cedex 13, France ∗
Corresponding author. E-mail address: [email protected] (T. Coton)
Please cite this article in press as: Bourgain G, et al. Hepato-peritoneal tuberculosis with negative interferon gamma assay (QuantiferonTM ) in an immunocompetent patient: A case report. Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2015.11.006