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Pleural TB

By Dylan Tierney Moderator Emeritus | 24 Oct, 2014

Greetings. I’d like to ask advice from the community about a challenging case that I recently saw in clinic.

The patient is a 35 year old woman with pleural effusion of unclear etiology.

She was generally well until developing acute onset malaise, fever and chills, shortness of breath, and right-sided pleuritic chest pain over the course of a few days. Evaluation at a community hospital revealed a normal white blood cell count but her chest x-ray showed a moderate right-sided pleural effusion. A follow up chest CT showed right lower lobe enhancing opacity that was consistent with atelectasis as well as small areas of non-enhancing opacity in right hilar region that could represent consolidation. Elevation of the right hemidiaphragm with small to moderate R sided pleural effusion was also noted. There were otherwise no clear parenchymal lesions.

The patient underwent diagnostic and therapeutic thoracentesis. Results showed that she had a lymphocyte predominant exudative effusion. The pleural fluid pH and adenosine deaminase were elevated. The pleural fluid was AFB smear negative and routine, fungal and mycobacterial cultures were without growth. Cytology was negative for malignant cells.

The clinical picture was initially felt to be consistent with possible para-pneumonic effusion but TB could not be excluded. The patient was treated w/ levofloxacin x 10 days. She had a positive interferon gamma release assay a few weeks after her presentation. A repeat chest x-ray at that time showed interval resolution of effusion. Sputum testing was negative in three samples. Results from sputum mycobacterial culture, however, are pending. She was then referred to me for evaluation.

She overall feels improved since her thoracentesis. She is back to work but continues to have an occasional dry cough. Her appetite good but has lost 1-2 pounds compared to before onset of illness.

She was born in India but has been living in the US for over 10 years. She has never had a tuberculin skin test. She has no known TB exposures or risk factors for HIV.

She is well appearing with normal vital signs and a normal physical exam.

I’m curious as to what the community thinks are the possible etiologic causes of the patient’s syndrome. What features are consistent with TB pleurisy in your experience? What features are contradictory? In my mind, I think she has around a 50% chance of her illness being due to tuberculosis. Is that estimate too high? Too low? What other testing would you consider to try to make the diagnosis?

I recommended empiric treatment for a presumed tuberculous effusion but the patient refused because she didn’t want to believe that she had TB. How hard would you push her to start therapy? What would be the regimen that you would recommend? Does anyone have experience treating these patients with less than four drug therapy for less than six months? How should I think about her risk of contagion while trying to convince her to start therapy?

Please let me know your thoughts. I greatly appreciate any insights you can share.




egh Eduardo Gotuzzo Replied at 12:49 PM, 24 Oct 2014

Dear Dylan
If 3 sputum are negative and culture also I feel is not necesary to start
Probably this is embolic subacute disease.also a cancer lesion special
breast cancer could be.also cRdiac insufficiency
Can mimic this presentation

Because if this case is tbc probably is a close case relete to
epidemiological issues and prevention
Meantime I will offer only clincal and Xry follow .up
Also in this case we prefer to avoid the use of quinolone because can be
negative the culture and sputum only because you usedlevofloxacin vir a few
ALSO s important to know how was the cells and proteins in pleural
effusion.in our hospital the culture of pleural biopsy show high level of
positive for tbc.
Eduardo Gotuzzo

El viernes, 24 de octubre de 2014, Dylan Tierney, MD, MPH via GHDonline <
> escribió:

Dr. Eduardo Gotuzzo
Director Instituto de Medicina Tropical "Alexander von Humboldt"

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Dr Lalit Kumar Anande Replied at 12:58 PM, 24 Oct 2014

Dear Dylan,

My advice do an ESR after her course of Antibiotics. Looks as a pneumonia causing effusion.

Please share her Xray and CT chest if possible


Dr Lalit Kumar Anande Replied at 1:00 PM, 24 Oct 2014

Please don't jump the guns for TB

Irfan Malik Replied at 1:08 PM, 24 Oct 2014

Do esr have any role in diagnosing TB

Vinaya Karkhanis Replied at 1:39 PM, 24 Oct 2014

Since Patient has clinically improved with antibiotics and thoracocentesis and had very acute presentation, it seems like bacterial or viral in ethology.
Since she lived in India almost for 25 years, just positive interferon test should not be considered for starting anti tuberculous therapy.
However, she can be kept under observation and if fluid refills, thoracocentesis and closed pleural biopsy can be attempted for AFB a culture for definitive diagnosis.
Starting anti tuberculous therapy against her will without evidence may not be very appropriate considering adverse effects of the therapy.
If she gets recurrent effusion, considering her age connective tissue disease needs to be ruled out.
CT findings mostly represent blesovsky's sign or comet tail sign of resolving pleural effusion.
Nice day,

Vinaya Karkhanis Replied at 1:40 PM, 24 Oct 2014



Dr Lalit Kumar Anande Replied at 1:49 PM, 24 Oct 2014

Dear Irfan,

This is an Age Old Investigation and the cheapest but still carries great value in letting us know the progress of TB during treatment.
It certainly is not THE PARAMETER but yet helps us a lot in pointing a finger at TB in case of confussion from other Latest and expensive investigations

Thomas John Replied at 1:57 PM, 24 Oct 2014

Dear Dylan,
I'll try to answer your questions to the best of my knowledge, from working
in tertiary care hospitals in India & Nepal:

What features are consistent with TB pleurisy in your experience?
- all her clinical features
-lymphocyte predominance, elevated ADA, positive IGRA & most of all history
of likely exposure (India)

What features are contradictory?
-short duration (though everything has start sometime); makes
para-pneumonic effusion likely

In my mind, I think she has around a 50% chance of her illness being due to
tuberculosis. Is that estimate too high? Too low?
-personally I feel the estimate is a bit low ~70%

What other testing would you consider to try to make the diagnosis?
-ESR might help, but non-specific and usually not elevated early in the
course of illness

How hard would you push her to start therapy?
-No point pushing too hard. Better to have her trust so that if she remains
unwell she will return, and she will be more willing then.

What would be the regimen that you would recommend?
Same as pulmonary TB. 2HRZE, 4HR

Does anyone have experience treating these patients with less than four
drug therapy for less than six months?
-never with less, only with more

How should I think about her risk of contagion while trying to convince her
to start therapy?
-Since she is sputum negative and only has extra-pulmonary TB, contagion
risk must be nil.

Hope this is helpful.

Tetyana Loginova Replied at 2:33 PM, 24 Oct 2014

Dear Dylan,

As you have mentioned this patient is from India, and was never
tested on tuberculin skin test. As most indian people she is vegeterian.
So immunity is not so strong.
I'd like to recommend GeneXpert test for sputum (quick PCR method).
Also I think we have to test her on a/b to HIV.

With best wishes,
Dr. Tatyana Loginova,
Kiev, Ukraine

Irfan Malik Replied at 2:39 PM, 24 Oct 2014

But it is clearly written in guideline ESR HAS no rule and diagnosis and monitoring of tuberculosis

Thomas John Replied at 2:39 PM, 24 Oct 2014

Another investigation that might be done is her Vitamin D levels.
I don't do it in, but colleagues in London do it as low Vit D levels seem
to correlate with decreased immunity and reactivation of latent TB...
especially in people with darker skin and decreased exposure to sunlight as
in this case.

Irfan Malik Replied at 2:43 PM, 24 Oct 2014

In my opinion you should go for pleuroscopy and biopsy of pleura under direct vision..send it for histolopatholgy and culture for AFB.

anita gaffari oskouei.MD Replied at 4:54 PM, 24 Oct 2014

İf İ become suspected via patient's symptoms,,,,first do an IGRA & ADA serologic test to not to delayind pt's golden time
since now 100% of my diagnosis were absulutly positive for both Tb related plueral and pericard regions

anita gaffari oskouei.MD Replied at 5:17 PM, 24 Oct 2014

it has a high mortality rate and, therefore, warrants early recognition and treatment,,,,making perfect and accellerated decisions is the golden key to pt's survival.....

Charlotte Hall Replied at 5:27 PM, 24 Oct 2014


A difficult case; I presume you are practising in the US and hence have access to relatively advanced diagnostic tests.

One question in my mind is how long is it since she initially presented; from my experience pleural TB can present acutely like this, but a parapneumonic effusion would too. The differential of an exudative pleural effusion I'd think about in this case would include malignancy or Meig's syndrome (seems unlikely if it is resolving spontaneously), autoimmune disease (does she have any other connective tissue/joint symptoms?), or (more unusual) diseases involving both parenchyma and pleura such as acinetobacter. If it is a while now since the last chest imaging I would be tempted to repeat the CT; if there is still a parenchymal lesion/effusion you could go for a pleural biopsy (tissue with highest culture yield if it is TB) +/- a bronchoscopy to get washings and samples for histology. Has she had sputum cytology done? It might also be prudent to do a GeneXpert PCR on her sputum; I don't think WHO s currently advocating doing PCR on pleural fluid but some centres are trying it - probably has a low sensitivity though. Has she had an HIV test?

I think if she has an ongoing effusion after you've done your best to exclude malignancy an empirical trial of TB therapy is not unreasonable; I'd use standard RHZE 6 month regimen. I'm not sure we can say she is strictly extra-pulmonary TB only if there is parenchymal disease on the CT, but is she is smear/PCR negative I would consider her to be pretty much non infectious to immunocompetent individuals.

Kind regards, Charlotte (ID registrar, UK)

anita gaffari oskouei.MD Replied at 5:34 PM, 24 Oct 2014

friend charlotte İf you mean me,İ am living in iran now,,but in a wealthy enviroment,

anita gaffari oskouei.MD Replied at 5:37 PM, 24 Oct 2014

You are right,,,but i mean diagnosis in just a couple hours,,,,

anita gaffari oskouei.MD Replied at 5:42 PM, 24 Oct 2014

maybe other coincidence occure alont with tb ,,,but here you must have a high knowledge about plain xrays,cause people mostly not accepting a HRCT,,,

anita gaffari oskouei.MD Replied at 5:44 PM, 24 Oct 2014

or An ECG maybe usefull in some,,,,so many ways

anita gaffari oskouei.MD Replied at 8:43 PM, 24 Oct 2014

TB clinically active ж

Positive culture for M. tuberculosis OR •
Positive reaction to TST or IGRA, plus clinical, bacteriological, or radiographic evidence of current active TB'
so your pt is an crrent active TB case group lll.

treatment ROUTİN with steroids and anti inflamatory

anita gaffari oskouei.MD Replied at 8:45 PM, 24 Oct 2014

Persons at Increased Risk for Progression of LTBI to TB Disease..

Populations defined locally as having an increased incidence of disease due to  M. tuberculosis, (including medically underserved, low-income populations). like india

anita gaffari oskouei.MD Replied at 9:07 PM, 24 Oct 2014

corticosteroid use are at elevated risk of tendon rupture,anti inflamatory users may have seizures,and prolonged Qt
seriously sideeffects.

anita gaffari oskouei.MD Replied at 9:22 PM, 24 Oct 2014

i mean Tavanic side effects with ur prescription

and finally if drainage fluid is aerosolized. Persons with TB pleural effusions may have underlying pulmonary TB that is masked on chest radiograph because the effusion fluid compresses the lung. These patients should be considered infectious until pulmonary TB disease is excluded.

sorry for my long reasoning...

Assefa Kebede Replied at 4:27 AM, 25 Oct 2014

Thank you for sharing!! lots of valuable comments are circulating. I would
agree with most who share the idea of pushing further to exhaust all
possible diagnostic methods, like doing pleural biopsy and BAL....,,,,
because one has to rule out malignancy before going to an empiric therapy.
from imaging point of view , I would ask why does the diaphragm elevated?
is it do to atelectasis or diaphragmatic paralysis?.... it would be nice
to share the CT and Radiographic images.
as one colleague commented , so long as there is paranchymal lesion , its
difficult to say this is only a pleural TB. but , it has been described in
literature that there is a possibility that a pleura TB could have
spontaneous resolution infrequently .

my recommendations;
- please share the image so that we could learn from it and share opinion.
- as its a while since she had her original image , please take follow up
- please look for the expansion of the lung after aspirating the fluid ,
so that the parenchyma will be better characterized.

kind regards!!

Nkunzi Herve GASHABUKA Replied at 4:55 AM, 25 Oct 2014

Very contributive ideas and insights. Elevated diaphragm? I will recommend
to do a Liver ultrasound and measure the Liver enzymes too.

Rakesh Biswas MD Replied at 6:21 AM, 25 Oct 2014

Thanks Dylan for starting this thread beginning with a case presentation. I
am tempted to share our own cases from India here. :-)

Let us know if the pleural effusion is persistent. If parapneumonic due to
acute bacteria pneumonia it dries up rapidly and becomes un tappable soon.
If you are able to easily tap it again after two weeks it is likely to be a
tubercular pleural effusion in India (but you would still need to exclude
other differentials such as the ones mentioned by Charlotte and i quote,
"malignancy or Meig's syndrome (seems unlikely if it is resolving
spontaneously), autoimmune disease (does she have any other connective
tissue/joint symptoms?), or (more unusual) diseases involving both
parenchyma and pleura such as acinetobacter."

amos oburu Replied at 12:07 PM, 25 Oct 2014

Dear Dylan, is a good experience to share in the community.
with my experience in the developing countries with limited resources, this patient qualifies for anti TB without further delay. we might not force her into medication as she may not adhere to treatment. but then the use of antibiotics like levofloxacins actually affect the diagnosis of TB, and may lead to missed TB cases.

Amos Oburu

Alberto Mendoza Replied at 12:29 PM, 25 Oct 2014

Hi Dylan and collegues,

Some comments regarding the case
1. The only feature that is not clear for TB is the acute onset. Really is it true? Maybe general symptoms as night sweats, weight loss or fatigue were present. If this is an acute onset It would be a complicated viral or bacterial pneumonia with pleural effusion, and in this case, a normal white blood count (without leucocitosis, at least) is very uncommon in a young immunocompetent patient. (is she HIV (-)?)
2. The other important feature is the positive ADA, a metha-analysis (attached file) show a positive likelihood ratio 9.03 (95% confidence interval 7.19-11.35) for ADA test and pleural TB. If Dylan thinks that 50% is TB, in a Fagan nomogram considering the positive likelihood ratio of ADA the diagnosis of TB increases to 90%, so that, a TB treatment is justified. Also is important for us the value of ADA, is it high? (more especific for TB)
3. I agree with professor Gotuzzo, here in Peru we have good answer with pleural biopsy, but I thing this is not feasible because she no longer has pleural efussion.
4. Also we are very careful to start quinolones with these patients, and we used to try them with doxicline or azitromicine if we consider a bacteria as a ethiological agent, and We continue working on TB diagnosis (at least two liquid culture in MODS assay or MGIT, and two concentrated smear per week until we get the culture results) Also as she has a parenquima lesion, Gene Xpert is important, and finally an endoscopy process must be done.
5. If this is an active parenquimal TB lesion, you must look for lesions with tree-in-bud appearance in TC.
6. The TB exposition in the last 2 years is very useful. Did she travel to Indian in that time? is she living with new relatives or firend from India with respiratory symptons?

7. Finally, If she is without symptons, you must follow working on her diagnosis, but if she again develops respiratory symptons you must start TB treatment.


Alberto Mendoza
National TB Program,

Attached resource:

Masoud Dara, MD Moderator Replied at 2:07 AM, 26 Oct 2014

I agree with Amos,
We need to be prudent with Levofloxacin, until TB is fully ruled out.

Emmanuel Samuel Sima Replied at 2:15 AM, 27 Oct 2014

Thanks for sharing..I suggest you offer an HIV test despite being low risk for HIV if the patient is found HIV positive then the risk for TB will be higher as well,.Pleural biopsy if can be done safely is very useful in this case
I also have suspicion for TB based on history of illness and history of living in India.She is probably getting better due to treatment with Quinolones which has antituberculous effect.

Quenesio Chipa Replied at 3:48 AM, 27 Oct 2014

Enviado a partir do meu smartphone BlackBerry 10.

Fikreselam Desalegn Replied at 9:07 AM, 9 Nov 2014

let's protect the quinolones!! specially the higher generations!

Irfan Malik Replied at 9:56 AM, 9 Nov 2014

Yes true respiratory quinolones are being used in Asia blindly

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