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Bilateral pleural effusion in a HIV negative patient – TB or not TB?
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Travel Medicine and Infectious Disease (2016) xx, 1e2
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
DIAGNOSTIC CHALLENGE
Q4
Q3
Bilateral pleural effusion in a HIV negative patient e TB or not TB? ¨la A.M. Huson a,b,*, Hillegonda S. Hermanides a, Michae Martin P. Grobusch b, Martijn Kross c a
Department of Internal Medicine, MC Slotervaart, Louwesweg 6, Amsterdam, The Netherlands Center of Tropical Medicine and Travel Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, The Netherlands c Department of Respiratory Medicine, MC Slotervaart, Louwesweg 6, Amsterdam, The Netherlands b
Received 10 February 2016; received in revised form 9 March 2016; accepted 22 March 2016
We saw a 30-year old male sailor from the Philippines, who was working on a ship that had moored in the Netherlands. He presented with a one-month history of productive cough, dyspnea on exertion, bouts of fever, loss of appetite and weight loss. He had no history of tuberculosis, and a routine chest X-ray obtained 4 months earlier was unremarkable. Physical examination revealed cachexia, fever (38.4 C) and tachycardia (111/min). On auscultation, heart sounds were normal. There were bilateral lung crepitations, most pronounced on the right side. There was no lymphadenopathy in neck, axillae or the inguinal region. Chest X-ray showed bilateral pleural effusions (Fig. 1); with the right-sided one being drained. Laboratory examination of the fluid revealed an exudate with a high lactate dehydrogenase content (1012 U/L) and elevated adenosine deaminase (120 U/L). Cultures of blood and pleural fluid remained negative. Additional laboratory tests showed no evidence of HIV infection or auto-immune disease (anti citrulline, rheumafactor and ANA negative). A tuberculin
* Corresponding author. Center of Tropical Medicine and Travel Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-105, 1105 AZ Amsterdam, The Q1 Q2 Netherlands. Tel.: þ31 20 566 6034. E-mail addresses: [email protected] (M.A.M. Huson), [email protected] (H.S. Hermanides), m.p. [email protected] (M.P. Grobusch), [email protected] (M. Kross).
skin test was negative and examination of sputum and pleural fluid by Ziehl-Neelsen and auramin staining, as well as Xpert MTB/RIF revealed no evidence of tuberculosis. Video assisted thoracic surgery (VATS) was performed to sample pleural tissue. Pathological examination revealed necrotising granulomatous inflammation; and the auramin
Fig. 1
Chest X-ray showing bilateral pleural effusion.
http://dx.doi.org/10.1016/j.tmaid.2016.03.010 1477-8939/ª 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Huson MAM, et al., Bilateral pleural effusion in a HIV negative patient e TB or not TB?, Travel Medicine and Infectious Disease (2016), http://dx.doi.org/10.1016/j.tmaid.2016.03.010
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M.A.M. Huson et al. Table 1
Differential diagnosis of exsudative, bilateral pleural fluid.
Infectious Bacterial/viral pneumonia Tuberculous pleurisy Intra-abdominal infections, including peritoneal tuberculosis Malignancy Carcinoma Lymphoma Mesothelioma Leukemia Chylothorax Paraproteinemia (multiple myeloma, Waldenstrom’s macroglobulinemia) Peritoneal carcinomatosis Auto-immune Lupus pleuritis Rheumatoid pleurisy Mixed connective tissue disease Other Liver cirrhosis Pancreatitis (acute, chronic) Acute respiratory distress syndrome Trapped lung (e.g. after pneumonia, rheumatoid pleurisy, uremic pleurisy, tuberculosis, and malignancy)
stain was positive for mycobacteria. Xpert MTB/RIF of the pleural tissue also demonstrated Mycobacterium tuberculosis without rifampicin resistance. First-line antituberculous medication was started with rapid resolution of symptoms. The patient was discharged on medication and returned to the Philippines. Four weeks after discharge, cultures of both pleural fluid and pleural tissue revealed M. tuberculosis with good sensitivity to all first-line antituberculous drugs. Pleural tuberculosis usually presents with unilateral pleural effusion. Bilateral pleural effusion is uncommon and predominantly occurs in immune-compromised patients, particularly in patients with HIV infection. Notably, bilateral pleural effusion can also be a sign of peritoneal TBC. The differential diagnosis of exudative bilateral pleural effusion is broad, as indicated in Table 1. However, as the Philippines are among the countries with the highest incidence of tuberculosis in the world (292 per 100.000), clinical suspicion remained high in our case. Diagnosing pleural tuberculosis remains challenging. The tuberculin skin test was applied as a screening test in our case. However, this test is limited by false-positive results due to exposure to non-tuberculous mycobacterial infections and prior BCG vaccination (specificity of 60e97% depending on prior vaccination), as well as false negative results in immune-compromised individuals and patients with active tuberculosis due to tuberculosis-induced anergy (sensitivity of 80%). The IGRA is a more specific and more sensitive screening test for M. tuberculosis (specificity >95% regardless of prior vaccination and sensitivity 90%), but can also be false-negative in immune-compromised patients. Neither of these screening tests provides a definite diagnosis, especially in patients from areas endemic for tuberculosis. Therefore, an additional IGRA was not performed in our patient. Ziehl Neelsen or auramin stains of
pleural effusions are usually negative. Nucleic acid amplification tests like Xpert MTB/RIF have a higher sensitivity for detecting both pulmonary and extrapulmonary tuberculosis compared to Ziehl Neelsen or auramin staining, and provide additional information on rifampicin resistance. However, Xpert MTB/RIF of pleural fluid still only detects pleural tuberculosis in a minority of cases, with a sensitivity of 34%. Notably, active parenchymal tuberculosis is common in cases with pleural tuberculosis, so sputum examination remains important. In our patient, cultures of pleural fluid and pleural tissue eventually became positive for M. tuberculosis, but sampling of pleural tissue allowed for a more rapid diagnosis and initiation of first line treatment guided by the Xpert MTB/RIF results. This case illustrates the limitations of initial non-invasive diagnostic testing, and the value of obtaining tissue for a direct diagnosis. Upon request, a literature list with relevance to the case discussed here is available from the authors.
Author contributions MAH and MK conceived the idea for the manuscript; MAH, HSH and MK were involved in clinical care of the patient; MAH, HSH and MPG were involved in the selection of relevant literature; MAH and MK drafted the first version of the manuscript; all authors reviewed and commented on the final version of the manuscript.
Conflicts of interest and source of funding The authors have no conflicts of interest to declare. No funding was received for the writing of this manuscript.
Please cite this article in press as: Huson MAM, et al., Bilateral pleural effusion in a HIV negative patient e TB or not TB?, Travel Medicine and Infectious Disease (2016), http://dx.doi.org/10.1016/j.tmaid.2016.03.010
63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124
TMAID969_proof ■ 5 April 2016 ■ 1/2
+
MODEL
Travel Medicine and Infectious Disease (2016) xx, 1e2
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
DIAGNOSTIC CHALLENGE
Q4
Q3
Bilateral pleural effusion in a HIV negative patient e TB or not TB? ¨la A.M. Huson a,b,*, Hillegonda S. Hermanides a, Michae Martin P. Grobusch b, Martijn Kross c a
Department of Internal Medicine, MC Slotervaart, Louwesweg 6, Amsterdam, The Netherlands Center of Tropical Medicine and Travel Medicine, Academic Medical Centre, Meibergdreef 9, Amsterdam, The Netherlands c Department of Respiratory Medicine, MC Slotervaart, Louwesweg 6, Amsterdam, The Netherlands b
Received 10 February 2016; received in revised form 9 March 2016; accepted 22 March 2016
We saw a 30-year old male sailor from the Philippines, who was working on a ship that had moored in the Netherlands. He presented with a one-month history of productive cough, dyspnea on exertion, bouts of fever, loss of appetite and weight loss. He had no history of tuberculosis, and a routine chest X-ray obtained 4 months earlier was unremarkable. Physical examination revealed cachexia, fever (38.4 C) and tachycardia (111/min). On auscultation, heart sounds were normal. There were bilateral lung crepitations, most pronounced on the right side. There was no lymphadenopathy in neck, axillae or the inguinal region. Chest X-ray showed bilateral pleural effusions (Fig. 1); with the right-sided one being drained. Laboratory examination of the fluid revealed an exudate with a high lactate dehydrogenase content (1012 U/L) and elevated adenosine deaminase (120 U/L). Cultures of blood and pleural fluid remained negative. Additional laboratory tests showed no evidence of HIV infection or auto-immune disease (anti citrulline, rheumafactor and ANA negative). A tuberculin
* Corresponding author. Center of Tropical Medicine and Travel Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-105, 1105 AZ Amsterdam, The Q1 Q2 Netherlands. Tel.: þ31 20 566 6034. E-mail addresses: [email protected] (M.A.M. Huson), [email protected] (H.S. Hermanides), m.p. [email protected] (M.P. Grobusch), [email protected] (M. Kross).
skin test was negative and examination of sputum and pleural fluid by Ziehl-Neelsen and auramin staining, as well as Xpert MTB/RIF revealed no evidence of tuberculosis. Video assisted thoracic surgery (VATS) was performed to sample pleural tissue. Pathological examination revealed necrotising granulomatous inflammation; and the auramin
Fig. 1
Chest X-ray showing bilateral pleural effusion.
http://dx.doi.org/10.1016/j.tmaid.2016.03.010 1477-8939/ª 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Huson MAM, et al., Bilateral pleural effusion in a HIV negative patient e TB or not TB?, Travel Medicine and Infectious Disease (2016), http://dx.doi.org/10.1016/j.tmaid.2016.03.010
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62
TMAID969_proof ■ 5 April 2016 ■ 2/2
+
MODEL
2
M.A.M. Huson et al. Table 1
Differential diagnosis of exsudative, bilateral pleural fluid.
Infectious Bacterial/viral pneumonia Tuberculous pleurisy Intra-abdominal infections, including peritoneal tuberculosis Malignancy Carcinoma Lymphoma Mesothelioma Leukemia Chylothorax Paraproteinemia (multiple myeloma, Waldenstrom’s macroglobulinemia) Peritoneal carcinomatosis Auto-immune Lupus pleuritis Rheumatoid pleurisy Mixed connective tissue disease Other Liver cirrhosis Pancreatitis (acute, chronic) Acute respiratory distress syndrome Trapped lung (e.g. after pneumonia, rheumatoid pleurisy, uremic pleurisy, tuberculosis, and malignancy)
stain was positive for mycobacteria. Xpert MTB/RIF of the pleural tissue also demonstrated Mycobacterium tuberculosis without rifampicin resistance. First-line antituberculous medication was started with rapid resolution of symptoms. The patient was discharged on medication and returned to the Philippines. Four weeks after discharge, cultures of both pleural fluid and pleural tissue revealed M. tuberculosis with good sensitivity to all first-line antituberculous drugs. Pleural tuberculosis usually presents with unilateral pleural effusion. Bilateral pleural effusion is uncommon and predominantly occurs in immune-compromised patients, particularly in patients with HIV infection. Notably, bilateral pleural effusion can also be a sign of peritoneal TBC. The differential diagnosis of exudative bilateral pleural effusion is broad, as indicated in Table 1. However, as the Philippines are among the countries with the highest incidence of tuberculosis in the world (292 per 100.000), clinical suspicion remained high in our case. Diagnosing pleural tuberculosis remains challenging. The tuberculin skin test was applied as a screening test in our case. However, this test is limited by false-positive results due to exposure to non-tuberculous mycobacterial infections and prior BCG vaccination (specificity of 60e97% depending on prior vaccination), as well as false negative results in immune-compromised individuals and patients with active tuberculosis due to tuberculosis-induced anergy (sensitivity of 80%). The IGRA is a more specific and more sensitive screening test for M. tuberculosis (specificity >95% regardless of prior vaccination and sensitivity 90%), but can also be false-negative in immune-compromised patients. Neither of these screening tests provides a definite diagnosis, especially in patients from areas endemic for tuberculosis. Therefore, an additional IGRA was not performed in our patient. Ziehl Neelsen or auramin stains of
pleural effusions are usually negative. Nucleic acid amplification tests like Xpert MTB/RIF have a higher sensitivity for detecting both pulmonary and extrapulmonary tuberculosis compared to Ziehl Neelsen or auramin staining, and provide additional information on rifampicin resistance. However, Xpert MTB/RIF of pleural fluid still only detects pleural tuberculosis in a minority of cases, with a sensitivity of 34%. Notably, active parenchymal tuberculosis is common in cases with pleural tuberculosis, so sputum examination remains important. In our patient, cultures of pleural fluid and pleural tissue eventually became positive for M. tuberculosis, but sampling of pleural tissue allowed for a more rapid diagnosis and initiation of first line treatment guided by the Xpert MTB/RIF results. This case illustrates the limitations of initial non-invasive diagnostic testing, and the value of obtaining tissue for a direct diagnosis. Upon request, a literature list with relevance to the case discussed here is available from the authors.
Author contributions MAH and MK conceived the idea for the manuscript; MAH, HSH and MK were involved in clinical care of the patient; MAH, HSH and MPG were involved in the selection of relevant literature; MAH and MK drafted the first version of the manuscript; all authors reviewed and commented on the final version of the manuscript.
Conflicts of interest and source of funding The authors have no conflicts of interest to declare. No funding was received for the writing of this manuscript.
Please cite this article in press as: Huson MAM, et al., Bilateral pleural effusion in a HIV negative patient e TB or not TB?, Travel Medicine and Infectious Disease (2016), http://dx.doi.org/10.1016/j.tmaid.2016.03.010
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