Thursday, May 15, 2014

Or .... then again ... maybe not.

Just heard back from the Chief of Allergy:
Hello Mr. Brooks,
Since our visit, I've been gathering more information on the lymphocyte toxicity testing.
I reviewed this with our immunology laboratory who confirmed there is no academic immunology lab in the US that does lymphocyte toxicity testing for drugs. It is not done anywhere here.
I corresponded with Dr. Shear who felt that Dr. Rieder who is the director of the Drug Safety Lab, Robarts Research Institute was excellent and a reputable laboratory. He didn't know though whether they had a validated version of the assay for Trileptal and Cymbalta.
I corresponded with Dr. Rieder the director of the laboratory. He felt they could test for Trileptal since it is an aromatic compound, but testing to Cymbalta would be very experimental. He is having his technician send the protocol. He asked for advance notice/scheduling as they are the only lab in North America with this capacity. I inquired about cost and he is getting back to me on that also.
So at this point, I am waiting the protocol from the tech. I envision these problems:

1. The need for a control being sent also. This is because the test itself is highly sensitive and the transport of the blood can cause changes in the cells that will alter the outcome. Without having a control sent from the same place and going through the same handling, it is difficult to interpret results.
2. Coverage of the test.
3. The experimental nature of the Cymbalta testing.

I expect to hear back from them later today and can update you. It may be easier to have this done at a later date and sent from a different office where the control etc can also be obtained. Our lab will not be able to do this.

Dr. Volcheck 

Can't ask for a more thoughtful and thorough reply.  But ... looks like this isn't going to happen.  Not here, at least.

I think I'm going to try to make a plan to fly out of here, this weekend.

This morning, Internal Medicine wrapped up with me.  In terms of getting sick so often, and having had multiple serious drug reactions, she said I'm "just not lucky."

In terms of moving forward .... with regard to meds ... she tends to agree with Dr. Volchek: try to be lucky in the future, and avoid meds.

If the lab really can't confidently test both drugs .... well ... it's nowhere near as valuable.

Not sure what I'm going to do, but ... I don't have any more clinic appointments -- just a dinner reservation at Pescara, early this evening.  After that, I'll check into logistics.

Ciao for now .... as always .... from ... The Gulag.

Wednesday, May 14, 2014

Allergy/Immunology, revisited

Ohhhhh-kay.  'Nother update.

Just met with the Chief of Allergy again.  This worked.  He didn't seem rushed.  He seemed very open.  My play went something like this:

"You've got a TON of patients to take care of.  I just have one: me.  I think I can add value, here."

Told him who I'd talked to, what I learned, and what I believed.  He said ... "I think that makes sense."  He checked my chart for when I had taken the anticonvulsant, and said ... "Yep.  That fits."

If at all possible, he will order the Lymphocyte Toxicity Testing.  The only place I knew of was up in the Toronto (Canada) area.  I showed him the PDF.  He jotted down all the relevant information.  As long as the Mayo lab can draw the blood, package it up appropriately, and ship it out appropriately ... we can get this done.  We'd plan to check the anticonvulsant AND the Cymbalta.

I talked to him about "neosensitization --" could I have become 'reactive' to other drugs taken during the same time.  He wasn't really aware of the concept, but took the time to look at the peer-reviewed paper that I showed him.  He thought the conclusions were sketchy, the sample size was very small, and that the risk was extremely low.  I actually tend to agree, but .... wanted to cover it out of an abundance of caution.

And ... I mentioned ... since THREE docs have now mentioned HIV as something that would explain my immune and medication reaction issues ... though I'm HIV-negative ... I said "It sounds like we're talking about some fairly serious immune problems, if they're consistent with HIV."

I asked him about evaluating my B-Cell and T-Cell function.  While my total lymphocytes are normal, he WILL check the B and T cells underneath that count.  Frankly, if there's an issue there ... nothing can be done about it, but ... I still want to know.  If you know what it's called ... you can keep track of ongoing research and developments.

When I explained my read on the history of my lab work regarding EBV and CMV, he agreed: the whole AHS/DRESS > immune suppression > viral reactivation thing ... fits perfectly.

This guy's sold.  Now, it's just a question of pinning down the trigger and staying FAR, FAR away from it.

Infectious Disease, tomorrow morning.  We have a few things to look for and discuss.  They may or may not merit treating.  Unclear.  I smell .... yet another blood draw ;-)

And then ... Internal Medicine.  I have to talk with her about things that follow AHS/DRESS, and ... not too UN-commonly ... like .... autoimmune diseases and something called "Fulminant Type 1 Diabetes."  

1 in 5 die from AHS/DRESS.  It's pretty serious.  It can have recurring consequences over the long-term ("sequelae").  I have to get a better understanding of what to watch for, how often, and with whom.

My family's oldest and dearest friends .... Barb and Don ... paid for me to go eat at the best-reviewed restaurant in Rochester, MN -- Pescara.  I'll do that tomorrow evening.  Wonderful people.  Really incredible gesture.  So ... if you're out there .... thanks SO much, Barb & Don ... as always.

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 ;-)

Tuesday, May 13, 2014

To Bi ... or ... not to Bi......

Minor update......

I got a call, yesterday, from the now legendary Dr. Yan Bi, GI Fellow.

Seems she accidentally ordered the stool specimen when she meant to order a blood draw.  She was only looking for one obscure thing -- alpha-1-antitrypsin deficiency.  Since that was all she ordered, they didn't look for infections ... or anything else.

Of course, if she had looked, that blood test had been done in California.  Hmmm.

She seemed pretty genuinely apologetic for her mistake.  I appreciate that.  She's young, though.  She'll learn ;-)

Perhaps more interesting ....

I told Dr. Bi that I was disappointed in Gastroenterology's unwillingness to consider an immune-mediated problem, and orchestrate a referral, or pick up the phone and call a Mayo colleague.  

"But we don't have any expertise in DRESS Syndrome or Anticonvulsant Hypersensitivity Syndrome."

I went on a bit.....

"I know.  I know you don't.  I get that.

But wouldn't you think somebody in the Mighty Mayo MIGHT know something about it ??  Isn't this a teaching hospital ?  Aren't you famous for collaborating inter-departmentally to try to puzzle through the tough cases ?  Even if it IS this DRESS/AHS thing ... because it HAS GI/liver involvement ... wouldn't it be a good thing for you guys TO recognize ??

I think it's the wrong move to send me to another GI guy in North Carolina when we haven't looked at the immune suppression > reactivation of latent virus > DRESS/AHS hypothesis.  I think there's a LOT more that could be accomplished here before bypassing all other options and sending me half-way across the country to yet another liver guy, particularly if he's 'just' a liver guy ... like the Mayo GI/Hepatology folks."

Dr. Bi was quiet for a moment, and then said .... "I actually agree with you."

Hallelujah.  That's uncommon among doctors, and probably even LESS common among Fellows at the Mayo Clinic.  You're not supposed to disagree with The Company.  

Again ... she'll learn ;-)

She went on to reiterate what my upcoming appointments looked like.  You're seeing Allergy, again, and then ......

"Dr. Bi: I'm really grateful for your call, your willingness to take responsibility for a mistake, AND your honesty ... but I know what my schedule is.  Thanks for all your help."

Dropped off the saliva/DNA specimen, and had a fasting blood draw, this morning.  Then, had to have my BP checked.  Despite two large coffees, 100/70.  Unfortunately, it still looks like I'm going to live forever ;-)

Going to have a BIG, greasy, NASTY hamburger for lunch, today.  If they have milk shakes, I'll probably have one of those, too.  That'll teach 'em ;-)

By the way ... having had not one drop of ETOH (alcohol) since 11/21/13 (I just checked the date), I've now asked a couple of the docs if they think I can safely have a beer, or a glass of wine, with dinner.  Nobody's biting.  They won't answer.  They just look at me.  

How dry I am ;-)  Cough, cough, hack, hack.....

Ciao for now ... from the blood-depleted, all-out-of-saliva, totally-cotton-mouthed satellite offices of ... The Gulag.

With admirably low blood pressure, I might add :-)

Monday, May 12, 2014

AAAAAAAaaaaaaaaaaaaaaaahhhhhh !!!

Walked for about 25 minutes, but was just too tired to keep going.  Came back to the room and passed out.

Woke up when the phone rang.  It was Mayo, telling me that Internal Medicine has referred me back TO the SAME Chief of Allergy that I saw ten days ago -- the guy who didn't want to run tests to figure out what drug tried to kill me.

That's special.

But that's not why I'm screaming out.

When I stopped in the lab to pick up my P450 DNA saliva specimen kit, I asked for help tracking down my lost stool sample test results.  

After a series of phone calls, the very helpful lab tech found out that the results HAD BEEN ready since my b'day (5/2), and in the system for the doc to review.

I've asked the doc three times if she's seen the results.  Nope.  The third time was this morning, before chatting with the lab tech.

This afternoon, I received the following reply from the doc:
I don't see any stool result. As a matter of fact, I don't see orders for stool.

Yes.  THIS is what I'm screaming about.

I called the Lab Tech.  Can you please tell me who ORDERED the stool test ?  Sure.  It was Dr. Yan Bi, the Fellow in Gastroenterology.

I told her what Dr. Bi wrote to me.  

Chris was very frustrated.  She's going to call Dr. Bi, and explain to her how to look up a lab result in their system.

I said ... "Chris ?  Somebody ordered this test, right ?  I mean ... you guys didn't just hand me a random specimen container, and ask me to give a stool sample, right ?  Somebody DID order this for me, right ?"

She laughed.  "Yeah," she said, "Dr. Bi ordered it.  I'll have to call the doctor and have a little chat with her."

Thanks, Chris.  Thanks a lot.

Mayo is a big system.  Big systems are imperfect and disorganized.  I know that.

But this piece has been hugely frustrating.  Dr. Bi is a student, and she's making some pretty rookie mistakes at my expense.

I also mentioned to Dr. Bi that I'm a bit disappointed that -- as the patient -- I have to self-refer to Internal Medicine, in order to get a more thorough approach to getting the correct diagnosis.

To that, Dr. Bi responded
Usually it is easier and faster for patient to get Internal medicine consult than referral from a specialty clinic.  
You have been evaluated by our allergy department who recommended checking HIV and IgG for you. You have also been evaluated by our genetic department who does not feel like you have a mitochondria disorder but recommend a pharmacist consultation. 
[Yeah.  I know what HAS happened.  We don't move the ball forward by telling me what I already know.]

What I don't know is .....

  1) Why nobody seems interested in finding out -- for sure -- which drug did this to me, when it seems infinitely possible and relatively simple

  2) Why a guy with a diagnosed IgG Subclass Deficiency isn't being evaluated when his total IgG level (the sum of the level of all the subclasses) dropped 15% through this liver crisis

  3) Why I wasn't given an appointment with somebody to 'manage' my care, from the beginning

  4) Why she doesn't think I ever took an anticonvulsant

  5) Why I NEED to self-refer for something (like DRESS Syndrome or Anticonvulsant Hypersensitivity Syndrome) if it fits the facts.  I can't believe a cancer patient has to decide that he needs to see radiation, oncology, surgery, infusion therapy, etc., for themselves, and then call each of those departments, try to convince them that he has cancer, and then beg for an appointment

  6) Why I have to work so hard to get HER the results for the test that SHE ordered, particularly when she swears she never ordered the test in the first place 

  7) Why the Genetic/Mitochondrial doc and the PharmD guy had to suggest the P450 testing (instead of Allergy or Gastroenterology/Hepatology).

Actually, Dr. Bi .... what HAS Gastroenterology/Hepatology done, so far ?  Told me that it was a Drug-Induced Liver Injury (I don't think so), and that I should go to North Carolina ?

So far, this is a very frustrating experience.  Let's hope it gets better as things move along......

Doing this medical thing is hard enough, Folks.  Fighting the system .... well ... that takes a fire in my belly that's been absent for too long.

Stay tuned.......

Movement ??

I got in to see Primary Care, this morning.  Yea !!

Next steps:

 - Cytochrome P450 testing (DNA test, from saliva)

 - referral to Dermatology (the ongoing skin issues, since the Christmas crash)

 - referral to Infectious Disease (look for 'hidden' infections, like Cytomegalovirus, Human Herpesvirus, Epstein-Barr Virus) that may have flared up and caused the hepatitis

 - referral to Immunology (try to figure it all out)

On Friday, I placed a call to, and spoke to, one of the two authors of THE book on Drug Induced Liver Injury.  

She was great.  

In short, she thinks my theory about DRESS Syndrome/Anticonvulsant Hypersensitivity Syndrome is a whole lot more likely than the Cymbalta thing.  She also thinks that the Lymphocyte Toxicity Assay (testing for which I've been pushing) is exactly the right way to be sure, since it's VERY accurate in determining a genetic, flawed response to anticonvulsants.

Also, I once had a fairly severe reaction to Bactrim (a sulfa antibiotic).  She was pretty sure there was "cross-reactivity" between Sulfa and anticonvulsants.  

That means ... those who react adversely to one are highly likely to react adversely to the other.

As I think I did.

I checked.  She was right.

She was SO great on the phone ... that she even said ..... "I don't think your case is all that complicated.  You probably should have the P450 testing, and should stay away from anticonvulsants and sulfa drugs."

[sounded eerily familiar to me, since it's pretty much what I've been saying ....]

I would still want somebody to look at the neosensitization thing, out of an abundance of caution.

This is the problem with Mayo's approach.  Rather than rule in/rule out that I have an immunological problem with anticonvulsants (that would explain everything), they found it easier to warn me off of any and all "non-essential" prescription drugs.

Still not sure how long I'll need to be here, but .... things are starting to move, once again.  

I'm just going to have to put North Carolina on hold.  They really want to enroll me in one of their studies, for which you need to be seen within six months of the liver event.  That would put it at late-June.  I'm not so much looking to be in a study, though, as I am trying to figure out what happened, why, and how to avoid it in the future.

Besides ... if I'm right (and I think I am), then this is really much more about Immunology than it is about Gastroenterology and Hepatology.

So ... hold that thought, UNC.

I also spoke to the lab, this morning.  The ... er .... stool sample DID get processed, and the results WERE put live.  They told me to get in touch with IT (basically) to figure out why neither I nor any of the doctors could view the results.

One day at a time.......

Ciao for now ... from ... the cool, rainy, overcast, and generally NOT Southern California weather of ... The Gulag.

Friday, May 9, 2014

My Mayo Liver Doc (not the Fellow) Weighs In....

AHS is not within my area of expertise.  I do believe you should be evaluated by someone who is well versed in drug induced liver disease as a starting point. Dr. Bonkovsky would be a good person to start with
Okay.  Let me see if I understand correctly.  You don't really know much about Anticonvulsant Hypersensitivity Syndrome, or .... DRESS.

I guess that doesn't bother me, per se.  It might not BE a Gastroenterology/Hepatology thing.

But it doesn't sound as though you gave it a moment's thought, huh ?  

Maybe another department, at Mayo, would know a ton about this stuff ?  

Maybe a referral in this area code or time zone is still better than a referral to a liver guy in North Carolina -- particularly if this was really immunological or infectious, rather than being a straight liver thing ?

Nope.  I'm staying in Rochester, and will keep camping out in the lobby until Internal Medicine sees me.  I think I need to be seen by an Immunologist AND an Infectious Diseases doctor.  I think that's easier here than it would be in North Carolina.

So that's the update.  I got a walk in, but it was cold, ominous and windy.  Passed out when I got back.

Tomorrow's another day ... here ... in the meteorologically imperfect Northern reaches of ... The Gulag :-)

Will probably just cry a bit .....

I think it's probably time.

Haven't gotten in, yet, to be seen by Internal Medicine.

But ... after sending a couple of concisely worded messages to the Liver Docs .... about Anticonvulsant Hypersensitivity Syndrome  (AHS) ... I just got a reply back from the Fellow:

"But, Mr. Brooks. You didn't take an anticonvulsant, did you ?

You're kidding me, right ??

Of course, I wrote back and immediately corrected this little situation, but .... it's emblematic of what I'm up against.

[Yeah, I'm advocating that we consider a diagnosis of Anticonvulsant Hypersensitivity Syndrome, even though I've never taken an anticonvulsant in my life :rolleyes:]

Meanwhile ... I checked yet one more thing, to verify the goodness of fit OF Anticonvulsant Hypersensitivity Syndrome: would the liver biopsy slides look ANY different if it were AHS or if it were Drug-Induced Liver Injury (DILI) ??

The answer is no.  They should look exactly the same.  Hmmm.

I'm now offering my physicians a light-hearted $100 wager that it WAS AHS, and NOT a DILI.  I know what testing is needed.  If Mayo will do the blood draw, I found one of the very few labs that can DO the testing.  

It is my intention NOT to leave Rochester, Minnesota (or to leave these good people alone) until my hypothesis has been clinically explored.

Been in the Lobby since 6:45am, today.  Only about 40 minutes left until today's standby session is over.  Doesn't look like Internal Medicine and I will meet, today.  I will arrange to stay another week .... later, today, and resume my rightful place in this lobby at 7am on Monday morning.

Ciao for now ... from .... the mildly-medically-frustrated reaches of ... The Gulag.

Thursday, May 8, 2014

Go, Tarheels ???

"You're a remarkably well educated patient.  Are you IN medicine ?"

"Not by choice, Doc ...."

And so it begins.

I'm being referred to another Hepatologist -- this one, at University of North Carolina.  I spoke with him, this morning.  As of right now, he concurs with the Chief of Allergy, at Mayo: don't take ANY drugs unless "there's a strong indication for doing so, and with considerable care."  

But ... I reiterated ... if this truly WAS caused BY the immunosuppressive effect OF the anticonvulsant I took in October ... reactivating a latent virus (or infection), then this was NOT a "pure" Drug-Induced Liver Injury, right ?

He agrees it's possible, and would have me be seen by their Infectious Diseases guru, along with their Liver Center.

For now, I'm sitting in Mayo's lobby, "flying standby" to be seen, if possible, by General Internal Medicine, and -- hopefully -- Infectious Disease.  May as well try to get my theory explored while I'm here.

The referral came about as a result of my cousin talking TO my Mayo Liver Doc.  The Liver Doc says the requisite testing is beyond the capabilities of Mayo.

But he's still talking about a clean Drug-Induced Liver Injury.  I'm not.  I need to be 100% sure (if at all possible) that this was NOT infectious before *I* believe it was purely drug-induced.  That may NOT be possilbe (being 100% sure), but ... if they DO decide that I AM infected with Epstein-Barr Virus or Cytomegalovirus or Human Herpesvirus (or similar), and DO find antibodies in my blood ... well ... we may yet prove it was NOT cleanly drug-induced, but ... rather ... immune-mediated, meaning .... just avoid EVER taking an anticonvulsant again, and you'll be okay.

Unless I've BECOME allergic ("neosensitization") TO any of the drugs that I was taking WHILE the Anticonvulsant Hypersensitivity reaction took place.  It happens.  It's documented.

My theory is a desperation move, but .... their theory is an extreme long shot, too.  My theory also implies I treat the underlying infection, if possible, avoid ONE class of meds, try to explore new allergy to the OTHER classes of meds, and ... maybe ... move forward with a longer leash than I have, today.

I'll stay in Rochester until I can be seen by Internal Medicine, and any other specialty they deem appropriate (eg, Infectious Disease, Immunology).  

Meanwhile, I'm gathering up my records, and will forward them to the UNC Hepatologist for HIS team's review ... once I'm finished at Mayo.

I'll be seen in North Carolina within a few weeks.  May go from here TO there.  Dunno' yet.

"Flying standby" means sitting in the lobby for hours each day, waiting for an opening in the schedule.  They think I could get in within a few businesss days.  I'll extend my hotel, and cancel my Saturday flight to hang out here a while longer.

Stay tuned.......

Wednesday, May 7, 2014


Sort of......

I have to whine, rant, and vent a bit (more)....

I probably got sick in early or mid-December.  Just ... pretty much stopped getting out of bed.  That's not like me.  I move.  I like to move.  I need to move.

Then came Christmas Day, when it HIT.

On 12/26, I had a scheduled Pain Clinic appointment, and I went.  Not a doc I knew, but I told him about the fever, chills, and dark urine.  He replied, "You should talk to a doctor about that."  It would have been funny sarcasm, but for the fact that it wasn't meant as either.

That day, I stopped into Primary Care, told them what was going on, and that I needed to be seen by a doctor.  January 15th was the first available appointment.  I probably should have gone to Urgent Care or the Emergency Room, but ... I was so tired ... I just didn't care.

We know what happened next, and it was bad.

By the time I was referred to Gastroeneterology (gut) and Hepatology (liver), it was February 5th ... almost six weeks later.

Yesterday's pharmacy guy and I agree: it's quite likely that the anticonvulsant I was given suppressed my immune system, and allowed some hidden infection to rage.

UC Irvine tested me for Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV), either of which could explain every aspect of what happened to me, AND how I'm feeling now.  In both, the test results indicated "past infection," but not "current infection."

So they blew those off.

In looking at those lab test results, Mayo blew those off, too.

But I awoke, this morning, profoundly exhausted ... with whole-body chills ... and went back to bed.  I never go back to bed.  I may WANT to ... but I don't ;-)

When I awoke, I put on my four-pound, fish-bowl glasses and tried to understand the EBV and CMV test results, asking myself .... how long does "current infection" SHOW UP in the blood before it looks like "past infection ??"

The answer was crystal clear: the markers for "current infection" fade to black within "a few weeks."  My blood wasn't tested for these things for six weeks ... from the worst of it (I don't really know what the first of it was .....).

When I had a severe reaction to an anticonvulsant in about 2004, it was believed that the med suppressed my immune system, and allowed some hidden infection to flourish.

When I had a severe reaction to the DPT vaccine in about 2007, it was believed that the vaccine had suppressed my immune system, and allowed some hidden infection to flourish.

In October ... against my better judgment ... I allowed the Pain Clinic to put me on a low dose of another anticonvulsant (to treat neuropathic pain).  I got sick immediately, and stopped taking the med.

Maybe I never got better ?  Maybe that's what set up the liver issue.

There's ample research that shows that anticonvulsants can suppress the immune system.  Other ample evidence says that you can BECOME allergic to ANY med you're taking during that "Anticonvulsant Hypersensitivity Syndrome" immune crisis.

If I can't take this further, with Mayo ... somebody ... somehow ... somewhere ... I'm going to leave Rochester, Minnesota wondering when the next bomb is going to go off.  All it would take is one more good sinus infection, and a course of antibiotics, and ... potentially ... BAM !!


I've now asked three departments if they will refer me to General Internal Medicine.....

UPDATE: Just got a call from the husband of the Rochester, MN cousins.  He works in Gastroenterology research, at Mayo (, as it turns out....).

Bless his heart .... 25 minute call.  I told him what was going on -- what we THINK, what we KNOW, and what I think (with which Mayo doesn't necessarily agree).  

In short, he agrees that this is neither a simple, nor clean, nor straightforward presentation of .... well .... damned near anything.  

[Can I get an 'Amen ?']

He can make no promises, but he's going to talk to the GI/Liver doc who saw me, and talk about how we can poke, prod, and look further -- "peel back the layers of the onion a little bit," in his words.

I haven't had a drop of alcohol since October.  I could use a drink.  Ditto some (more) junk food.  I eat too darned healthy.....

Maybe a burger, fries, and a Coke for dinner.  Take THAT, liver !!!!

Ciao for now ... from ... the still confused, and existentially weary, offices of ... The Gulag.

Tuesday, May 6, 2014

The Wind Just Changed Direction ... if only slightly.....

This is the way it goes .....

I just met with ... Medications Management (or something like that) -- a really cool guy with his Pharmaceutical Doctorate degree.  

USUAL CAVEATS: Long story short, my words -- not his, but .....

He doesn't know why Mayo booked me with Gastroenterology/Hepatology, and NOT a Primary Care doc to coordinate all of this (neither do I).

He thinks I NEED to be seen by a "really good" Infectious Diseases guy, since he believes some of these med reactions HAVE suppressed my immune system, and could EASILY have reactivated some underlying virus or infection.

Of course, HE can't refer me to any of those groups, but ... more on that, later.

He went through all the meds with me ... to which I'd had noteworthy adverse reactions, and ... using the Up-To-Date website ... we evaluated how each was metabolized.  The Cytochrome P450 enzymes are largely responsible for breaking down things like drugs.  

In humans, it's believed there are about 57 such enzymes that matter.

Each of the main meds to which I've had an adverse reaction, and ... all five of the meds I was on when the Christmas thing happened ... are metabolized, at least in part, by one or more of THREE different CYP enzymes.

It looks like they (Mayo Labs) CAN run genetic testing (to look for disorders) for those three CYP enzymes.  Doing that is a no-brainer.

It looks as though Mayo can test for a number of OTHER CYP enzymes (to see what other classes of drugs MIGHT kill me).  That is a no-brainer to me, but will undoubtedly take me fighting with Mayo and/or my health insurance carrier.

It turns out I have a cousin, here -- a retired Administrator from Mayo.  It turns out ... her husband is a Mayo Gastroenterologist/Liver Doc.  I've reached out to them, and should talk to them tomorrow.

The PharmD's notes are going to be sent back to the Genetic/Mitochondrial doc.  She (the Mito/Genetic doc) referred me to Pharmacy.  That's how it works.  She would also have to decide what testing to order, and order it.

I'm going to have to push for a few things .... probably starting with Gastroenterology, and HOPEFULLY with my GI doc cousin's assistance:

- a referral to a GREAT internal medicine doc ... hopefully leading to

- a referral to a GREAT infectious disease doc, and

- as much of the P450 testing as I can get

Mayo's been tough, Folks.  They were tougher than me last time, and they're tougher than me this time.  I've been pretty darned sick, and really darned exhausted.  There's no fight left in me.

This PharmD guy .... rekindled a tiny ember .... not yet a spark ... but a tiny ember in me.  

He was my last scheduled appointment (outside a 5/12 Psychology app't that I was leaning toward canceling).  When he asked me what was next on my schedule, I told him that: nothing.  He seemed genuinely and deeply troubled by that ... FOR me.

This isn't likely a game changer.  The most it does is support my long-standing belief that:

- I have something very basic wrong with my immune system

- I have some underlying infection(s) that recur during times of stress

- I have some problem with how my body processes medication

Figuring out something in the infection group .... as always ... points to meds to treat.  That puts me squarely in the face of that third problem ... again.

Getting these referrals won't be easy.  

Getting the reasonable and appropriate testing authorized and ordered won't be easy.

Getting a solid diagnosis(es) won't be easy.

Treating whatever they do find won't be easy either.

But at least I had one guy who basically said to me: don't go home.  Don't give up.  Not yet.  It's not over yet, or ... at least ... it shouldn't be.

Stay tuned.....

Monday, May 5, 2014

Another day, another doctor :-)

I met with the Mitochondrial/Genetic doc, this morning.  

Nothing particular accomplished.

I don't fit the profile, at all, of having a primary Mitochondrial Disorder.  Neither does she think there's reason to check FOR secondary mitochondrial problems that may have been drug-induced.

She basically said ... she doesn't think mitochondrial problems explain my situation, and that ... even if genetic disorders do ... we've only sequenced the genomes of about 7,000 of the probably 22,000 genes, and there's nothing actionable to be done, even if they DO find genetic issues in me.

Translation: it's expensive testing, and you don't seem to qualify.

Although she couldn't honestly say how much of my drug reactions were 'metabolic' (how drugs are metabolized by the liver) versus 'allergic' or 'immune-mediated,' she did recommend I get P450 testing, and referred me to Pharmacy to see if they'll order it.

It's one of the tests that Allergy/Immunology deemed not worth doing.  They were probably right, but .....

This afternoon, I was seen by Ophthalmology.  

The ophthalmology technician couldn't measure the alignment problems of my eyes.  She finally said that ... if I wasn't seeking an eyeglass prescription from Mayo ... could we skip this part ??  Yeah.  My eyes are vexing to most eye doctors.  The alignment issues are very rare, very unstable, and can change from minute to minute ... like the focusing issues. 

The opthalmologist said what they always say: your eyes are bone dry, but do not show obvious signs of 'corneal staining --' true pathology ... scarring ... frank disease.  The corneas did not seem swollen.  No obvious meibomian gland dysfunction or blepharitis.  

He didn't seem to know much about Corneal Neuropathy, but understood my .... er ... discomfort.

He also said he saw enough loose conjunctival tissue (conjunctivochalasis) to understand why scleral lenses were no longer an option.  He mentioned the chalasis surgery, but said it has its own inherent risks, and that .... as I've heard ... the chalasis is likely to return, particularly with the amount of suction a scleral lens MUST have in order to stay in place.

He went over all the basics about lubricating drops, punctal plugs (mine are all cauterized), fish oil, moisture goggles, humidifiers, etc., etc., etc.  Very nice guy, but I just smiled and nodded.  You're only looking at my eyes with a 40 power microscope, Doc.  Get your hands on a confocal microscope, and check out my corneal nerves at 1000X maginification, and THEN we'll talk ;-)

But there was a clear positive, today: I walked for almost an hour AFTER Ophthalmology (with my eyes fully dilated, and clamped 99% shut in the Minnesota sunshine), and ... rather than need to collapse on the bed .... had enough energy to stop for a nice dinner before heading back to the hotel.  

It was a moment, and I had to be grateful for it.

When I got back to the room, I saw a couple things on my Patient Portal website: the reports from Pathology's review of my liver biopsy slides and the report from Radiology from my abdominal ultrasound.  Long story short ... it just looks more and more like it was a drug-induced liver injury, attributable to Cymbalta.

While most alternatives would be worse .... this one DOES mean ... that the whole "prescription meds" thing is now INFINITELY complicated.  In some ways, a worse diagnosis would have been simpler.  

I've been saying that since Christmas.  Nobody really agrees, but .... hey.

But I don't think I can wonder, much longer, whether or not it was drug-induced.  I think I'm sold.  

Still awating all the ... er .... stool sample results and Radiology's review of my ORIGINAL MRI images where they saw a 'stricture' in my hepatic bile duct.

The results of my Total IgG came back significantly lower than they were in January.  Should we test for the IgG Subclasses ... which is the basic nature of my Primary Immune Deficiency (IgG Subclass Deficiency) ??  The Immunologist said no.  My total IgG wasn't low enough to merit checking the subclass levels, even though .... if it was my already-deficient subclass levels that fell further ... that might explain the ongoing infections.

Nope.  Sorry.  Not gonna' do it.

The culture test came back on the snot found in my ethmoid sinus.  Staph Aureus.  Aware of my drug issue, the ENT is prescribing a kind of antibiotic ointment ... that I can dissolve in a saline irrigation solution ... and use to rinse out my sinuses a couple times a day.  I'll buy the stuff tomorrow and start on it.

So ... yeah ... sinus infection.  That wasn't a surprise either ;-)

The tired has set in.  The dry room is searing my poor peepers.  Gotta' put my prescription swim goggles on ... watch TV ... and go to bed early.

Another day down ... with just a hint of style and grace ... here ... in the Gulag.

Friday, May 2, 2014

Give me Ham on Five, Hold the Mayo....

Reference from the movie, "Airplane."

Happy 50th to me !!!  Nah.  I didn't do anything.  Nah.  I may not.  If I'm less tired over the weekend ... maybe something.  Not today, though.

Been at Mayo a few days now.  Here's the long and the short of it:

They still think whatever happened to me was a Drug-Induced Liver Injury, and that the Cymbalta did it.  That's their best guess, plain and simple, but everybody agrees: that's it.

Radiology is still supposed to review my MRI images from UC Irvine.

Pathology is still supposed to review the biopsy slides.

My platelets were low again.  My spleen is enlarged, but the liver doc didn't notice that until I pointed it out to her.  Is this all because of the liver injury ?  Do I need to be monitoring my platelets ?  Shouldn't this have been over and better by now ?  Does any of THIS explain any of the ongoing symptoms ??

They don't know.

I don't think the liver docs have any direction, yet, from the Drug-Induced Liver Injury doc in Indiana, about testing.  Still waiting.

Fairly long visit with Allergy and Immunology, this morning.  My words, not his, but I promise you it matches up with the substance of what he said:

 - In most people with a drug allergy, they have ONE class of reaction and/or it's a reaction to ONE class of medications.  I've had several different reactions to several different classes of medications.  That makes me a very odd duck or an HIV patient (but I don't have HIV; was tested in January; told them to test me again, just to be quadruple sure).

 - He more than agreed with me about their drug allergy testing.  He didn't think it was worth doing.  It's not even right half the time, and it isn't particularly actionable because of that.  It also does NOTHING to account for being on more than one med, or one med over time.  We agreed not to spend the $$.

 - He agrees that -- since each drug event WAS worse than the last -- the stakes are now incredibly high.  Ticking time bomb.  No way to predict what will happen, how bad it will be, or when it might get triggered, but it is reasonable to guess the next one could easily be Very Very Bad.  He mentioned SJS/TENS, and began to explain them to me.  No need, Doc.  I've met a few handfuls of SJS/TENS patients.  Breaks your heart.

 - His advice to me was "If you don't _absolutely need_ a medication, I wouldn't take any."   Then he thought about it a bit and said, "I guess that's easy for me to say, isn't it ?"  I laughed.  "Yeah, Doc.  That's easy for you to say.  I have a banged-up immune system, chronic neuropathic pain in my eyes and Complex Post-Traumatic Stress Disorder."

 - They still don't think the IgG Subclass Deficiency is "it."  They see too many perfectly healthy people with the same Subclass Deficiency who show absolutely no symptoms.  That's what they told me seven years ago.  The thinking really hasn't changed.  Not at Mayo, at least.

 - I asked him for a referral to Psychology, if they had people who specialized in chronic medical conditions that had a profound impact on patient quality of life.  He was going to refer me to Psychiatry until I said .... "Nah.  They usually just give pills.  I'm allergic to pills."  I got the Psychology referral, but it's on 5/12 -- two days AFTER I'm scheduled to fly out of here.  May stay in the area, though.  Have to think about it.  Have had no luck thinking even a day out, lately.  Not even a few hours out.....

Had an abdominal ultrasound this afternoon, and had to drop off a stool specimen for the lab.  Waiting on a fair amount of blood work to come back from the lab, now.  Probably Monday afternoon.

This afternoon, I saw the Ear, Nose, and Throat guy.  Pretty sure he's the one I saw, here, in 2007.  He 'scoped' me.  BIG yellow glop of infectious material in my right ethmoid sinus.  He was able to suction it out, and will send it to the lab.  Anatomically, my sinuses are plenty open and not ridiculously inflamed.

Just ... infected.

But ... he said ... when the results of the snot study come back from the lab ... what should we do ?

He won't prescribe me an antibiotic, having learned what we now know, and won't prescribe me an antifungal for the same reason.

He wasn't surprised that my trials of steroids and nebulized [antibiotics, steroids, antifungals, and NAC] didn't work.  I'm just one of those patients who they really can't fix or manage, and don't know why I'm as bad as I am with recurrent infections and recurrent nasal polyps.

I asked him if sinus infections - left untreated -- WILL eventually resolve.

Not for everybody, but ... for the most part ... yes.  "But a guy like you could feel pretty miserable for a few months, if you can't treat a sinus infection."

Yeah, Doc.  I have that feeling, too.

Can the infections migrate, and become serious and potentially deadly ?  Yes, but that's very rare.

I didn't review the irony of that statement (ie, every issue I HAVE is rare) with him.  Why bother ? ;-)

He thought I should try a Xylitol based nose spray.  Not likely to help, but shouldn't hurt anything.

Monday morning, I WILL meet with a Genetic/Mitochondrial doc.

My vision has been very blurry, here.  I'm certain it's' the dry, heated air.  A stable tear film layer is critical to the whole focusing system.  You dry out a banged-up cornea and you get more blur.  Mine are very dried out.  Nonetheless, I'll also be seen by Mayo Ophthalmology on Monday.  They aren't all that good, in my experience, but ... what the heck.  I'm here.

This is kind of the end of the line, Folks.  I can think of nothing left to do ... nobody left to see ... nothing left to try.

 - Pray the pain away ?

 - Pray the PTSD away ?

 - Pray I don't get sick again ?

 - Just ... survive and exist until my energy starts coming back and I can DO something again ??

The odds .... are definitely not in my favor.

International travel seems ridiculously risky, now.  If I get sick overseas, I used to go see doctors and take the pills they gave me.  Now ... not quite so much.  Probably have to buy a MedicAlert bracelet, too, if they make any that say "No Meds !"

Oh ... maybe I could go spend six months living by the Bastyr Naturopathic College, up in Washington, and just pay them to try to rebuild my health, from the ground up, their way.  Maybe.

Everybody agrees with me that a lifetime of meds ... set against a basically fragile constitution ... and an unbelievable amount of sickness, medications, stress, pain, and surgery since the Colorado thing happened ... could easily have banged up my mitochondria pretty badly.

Yet another case of banged-up armor ... dramatically weakened defenses.

So ... while I DO want to know ... whatever I CAN know ... everybody agrees, so far: none of this is 'actionable.'  None of this can be treated.  The way things look, the box that defines my life is just profoundly small.  Claustrophobically so.

There wasn't a lot of upside to being optimistic about this trip, so I wasn't.  It's playing out as I guessed it might, plus or minus some Monday Morning Miracle on Mitochondrial Street (no way).

In my hotel room, I've mostly had to wear my prescription swim goggles to keep the dry air from further stressing my eyes.  But they fog up quickly, and ... I see very poorly out of them, so I'm getting very far behind on e-mails.

Sorry :-(

While I haven't been "sleepy," I've been maddeningly exhausted.  I walk to my appointments, and pretty well manage a 20 minute walk, twice a day, outside, but ... after that ... I collapse on the bed and stare dumbly at the television.

I'm eating well, but not much.  No appetite.  Losing weight again.  Que sera sera.

Fleegle The Frog is here.  My faithful sidekick.  He keeps his spirits up -- somehow -- no matter how dicey things seem.

Frog power, indeed.....

So ... Ciao for now ... from the 5th floor hotel room ... across the street from ... the Mayo Clinic offices of ... The Gulag.