Measuring Inflammation

Remember those old childhood cartoons where a guy hits his thumb with a hammer?  The thumb turns bright red, swells to three times its normal size, and hurts so much that painful rays emanate for all to see.

I remember the day I awoke in excruciating pain, my entire hand red and throbbing as if it was a model for one of those old hammer-to-thumb cartoonists.  In the cartoons, it’s funny – not so much in real life.

There have also been times my hands swelled to a lesser extent – not enough for anyone else to notice, but enough that it cut off the circulation in my ring finger.  When fingers swell so much that a perfectly sized wedding ring cuts off circulation and the finger turns blue, it’s a safe bet that there’s a fair amount of inflammation going on.

One would think that a doctor could write “significant swelling” as documentation of such events, but doctors seem to have a preference for numbers to quantify everything, including inflammation.  ESR (erythrocyte sedimentation rate) and CRP (C-Reactive Protein) are two lab tests that can be done to “measure” inflammation.  Unfortunately, those tests aren’t perfect.  People can have significant inflammation but perfectly “normal” lab results.  How ironic that someone’s feet can be too swollen to fit into shoes, hands can be too swollen to do anything, and a doctor can say, “I’m sorry, but according to your lab work, there is no inflammation.”  Many RA patients have “normal” inflammatory markers – accompanied by enough disease activity that joints are destroyed.

I’ve wondered why, if pharmaceutical companies can develop drugs to inhibit TNF-α, nobody can come up with a test to measure TNF-α in the bloodstream.  Same with interleukin-6 and the other proteins that are thought to be associated with disease activity in RA.  If numbers are so important, there should be a way to measure those things.

Scientists have been working on it, and have a new test.  This test doesn’t diagnose RA, but gives the doctor an objective number to indicate how active the RA monster is.  Announced late last year, the Vectra Disease Activity Test measures twelve proteins, applies a convoluted formula (take the logarithm of 1+CRP, multiply by .36, add the square root of this, multiply by that…) and produces a single number to quantify disease activity.

Yay!  With luck, this will be a better test.  Questions remain, though.

Given the number of RA patients with normal CRP, I don’t understand why that information is used in the new test’s calculations.  The testing company’s website compares the results to DAS28. I’d rather see some comparisons that show Vectra DA to be superior to existing tests.  What I’d really like to see is data from hundreds of RA patients with obvious disease activity but normal ESR & CRP, and see that this new test returns a high number, regardless of the normal ESR/CRP.  Show us the data.

Tuberculosis Testing & Methotrexate

Remember those old television commercials showing kids playing with their alphabet soup and AlphaBits?

I think that the scientists who write about tuberculosis miss the days of their childhood spent playing with their food.  There sure are a lot of mixed-up letters in the literature on this topic!  The DTBE of the CDC established the TBESC for purposes of TB research.  How accurate is PPD in people who’ve had prior BCG?  Is IGRA more accurate than TST?  What is the difference between T-SPOT.TB and QFT-G?*

Whew!  By now you’re asking (if you’re even still here), what does all of this have to do with methotrexate, anyway?

There are a zillion hoops to jump through before starting methotrexate:

  • lab tests
  • chest x-ray
  • tuberculosis test

Yep.  The rheumatologist should make sure that you don’t have TB (or LTBI) before prescribing mtx.

I was curious, because I remember my rheumy saying that I needed a TB test and silently groaning to myself, “Oh, no!  That means I have to come back here in a couple days to have it read.”  With a skin test for tuberculosis, a needle is used to inject a small amount of tuberculin purified protein derivative just beneath the skin, making a tiny red bump (a little bit like an insect bite).  Then, a couple days later, the person being tested must return so that a nurse can look at the little bump, measure it, and exclaim over its progress (or, hopefully, the lack of progress).  It’s not very convenient – but much more convenient than dealing with the disease.

Event though my doctor said I needed a TB test, and wrote TB on the lab slip (in addition to all the regular tests ordered), a skin test wasn’t done.  After a one-hour drive to the doctor’s office, a long wait because she was uncharacteristically behind schedule, then waiting forty minutes at the lab for a blood draw, and adding another hour in radiology for x-rays, I still faced an extra hour to drive home… I was exhausted!  I just wanted to get home and was quite willing to address the need for another test on a different day, so decided not to ask any more about the TB test.

Fortunately, a few days later my lab results showed up.  I discovered that there is a blood test for tuberculosis.  I’d only known of the skin test.  In fact, there are (at least) two blood tests for tuberculosis.

These tests are considered interferon-gamma release assays (IGRAs), and are performed in a test-tube on a blood sample.  Both tests appear to be more accurate than the skin test.  You can read more about it at MedPage Today

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  • TB:  tuberculosis disease
  • LTBI:  latent tuberculosis infection
  • BCG:  Bacille Calmette-Guérin (tuberculosis vaccine)
  • TST:  tuberculosis skin test
  • PPD:  purified protein derivative (another name for the skin test)
  • AFB Culture:  Acid-Fast Bacillus smear and culture and sensitivity
  • INH:   isoniazid (antibiotic to treat tuberculosis)
  • MDR TB:  Multi-Drug Resistant tuberculosis
  • XDR TB:  Extensively-Drug Resistant tuberculosis
  • TBESC:  Tuberculosis Epidemiologic Studies Consortium
  • IGRA:  Interferon-Gamma Release Assays
  • QFT-G:  QuantiFERON®-TB Gold
  • TSPOT/ T-SPOT.TB:  blood test that counts the number of effector T-cells that produce gamma interferon