To TB or Not to TB – That is the Question

So today was a definite win!  Whenever I’ve been asked for my assistance on a case by a physician who has never asked before I always call it a win. [Insert happy dance!]

This request came from a very respected Infectious Disease physician who currently has two possible cases of tuberculosis uveitis (translation for the muggles: tuberculosis infection of the eye).  The conundrum of this is that this physician hasn’t seen a case in more than 10 years and here are two possible cases at the same.  Yes, that is weird, especially for a condition that is exceedingly rare.  Here is a run down of the two cases:

  1. 66 year old female who had a PPD screening in February 2017 and another PPD screening in March 2017 both negative prior to volunteering at different facilities.  She then developed uveitis in mid-May, had a Quantiferon Gold TB test that was positive and a repeat Quantiferon test two weeks later that was also positive.  No apparent exposure to anyone with TB, no previous oversees travel, no risk factors … at all.
  2. 85 year old male who developed uveitis 3 months ago.  He had a Quantiferon test that was positive, then two more repeat tests that were both negative.  He did serve in the military oversees but that was 50 years ago.  No other apparent exposure to anyone with TB and no other risk factors.

So, the question is: Do they both have TB?  or … does one have TB but the other doesn’t? or … does neither have TB?

Most TB cases are respiratory and a chest CT can confirm the likelihood of a patient truly having TB, but these are not respiratory infections so a CT would not be of any assistance.  It should also be noted that neither of the patients started receiving treatments yet because treatment for TB is very long (like months long) and chronically has significant side effects so you don’t want to start treatment unless you really need it.  Additionally, neither of these patients really had any risk factors ………………… so what is your answer?

OK – let’s look at patient number 2 first.  He had one Quantiferon that was positive and then two more that were negative.  If you know anything about Quantiferon tests is that they are VERY sensitive to preanalytical specimen collection errors.  They are also very sensitive to the bench scientist’s technique.  So, given that two out of three were negative, and the Quantiferon test has a known issue of false positives due to both the preanalytical and technique errors, it is more likely that this man does not have TB and something else is causing his uveitis.

Now let’s look at patient number 1.  She had two Quantiferon positive tests so you might think that this is a real positive.  But she had them done not very long after having not just one, but two PPD skin tests.  There is something called a “boosting phenomenon” that causes the Quantiferon Gold TB skin test to be false-positive after recent PPD skin testing – and she had the PPD skin test done twice.  This puts into question both of the Quantiferon positive tests results and increases the likelihood that they are both false-positive.

Now you might be thinking “Gee, it sounds like your saying that neither one of them likely have TB.”  Well, with virtually no risk factors, it is highly unlikely that either one of them does.  So … what is causing the uveitis?

Upon further questioning of the patient’s history it is revealed that they both do have something in common: cats.  What is the most common cause of uveitis?  Toxoplasmosis.  What is a very common host reservoir for toxoplasmosis? Cats.  So why did this Infectious Disease physician jump to TB first?  Because both of these patients were referred to this facility after having the initial positive Quantiferon tests.  With the view of these test results it almost acted like blinders on a horse.  Now there are also other causes of uveitis, such as herpes-zoster, herpes-simplex, and CMV, but given that both patients have known exposure to cats, toxoplasmosis jumps to the top of the differential diagnosis list.

The mutual decision was made to do toxoplasma IgM serology on both patients.  We will wait for the results.  Perhaps we may have to look at the viral causes, perhaps not.  The physician said they will also consider a vitreous fluid Mycobacterium tuberculi PCR test (for the muggles: they will remove fluid from the inside of the eyeball and test to see if this bacteria is floating in it) if the toxoplasma serology is negative.  If the serology is negative, the vitreous fluid would be the only way to effectively rule out a TB infection, but really – who wants their eye fluid removed if they don’t have to?


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