Wednesday, May 14, 2014

The Biopsy Guru Weighs In.....

Dr. David Kleiner, of the National Cancer Institute, and a member of the Drug-Induced Liver Injury Network just weighed in:
The short answer to your question is that it is not possible on the basis of histology alone to distinguish duloxetine DILI from the liver injury you see in DRESS because neither is a specific thing.  Particularly DRESS or AHS, which are a constellation of systemic findings and liver injury that fall into the broad category of immunoallergic reactions.  The pathologic changes one sees in such cases include the changes we observed in your biopsy as well as a variety of other patterns.  When we tried to identify our immunoallergic cases in DILIN we ran into problems of case definition, because so many patients had various combinations of eosinophils in the blood, skin rashes and fever that a distinct population didn’t stand out.  Duloxetine does appear to cause an immunoallergic reaction, so it’s not clear to me that it can be excluded even if criteria are met for DRESS.   
I think this is a pretty helpful additional piece of evidence.  If the AHS/DRESS event did/does look different, when the liver biopsy specimen is viewed by a pathologist, then we could have effectively ruled it out.

But it doesn't, so we can't.  That's something.

Now ... if one of these two drugs was going to cause an allergic reaction, it is HUGELY more likely to have been the anticonvulsant than the SSNRI, because:
  1. 30+ years of data says so
  2. I've never had a reaction to Cymbalta before, and I've been off and on it for years
  3. I DID have an allergic reaction to sulfa.  Remember: those who are reactive to sulfa are quite often allergic to anticonvulsants
  4. I also had a serious reaction to Gabapentin, ALSO an anticonvulsant, though a different class
Let's be realistic, Folks.  If the glove doesn't fit ... you must acquit ;-)

I'm waiting for my 2pm app't with the Chief of Allergy.  This is helpful.

If I can't persuade him through good looks and charm alone, I'm going to try to get him to phone this guy.  He wrote the book on AHS/DRESS, and knows all about the relevant testing.  Test me to BOTH drugs, and see to which one(s) I react.

If it's only one, it's a slam-dunk.

If it's neither or both ... well ... pffft.  We're still confused ;-)

I'll also tell him about my Friday conversation with Dr. Laurie DeLeve.  Yeah.  I'm a name-dropper.

After this morning's app't, I walked the skyway a bit, eventually walking up 14 flights in a Mayo building.  I also just walked up the 15 flights to my Allergy appointment.

One step at a time ... right here ... in the slightly diaphoretic, overworked alveoli of ... The Gulag ;-)

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