Arthritis associated with anti-PD1

Here's a bit from a post I made in September regarding my check-up at Moffitt, then 15 months after my last dose of Nivo and 45 months after starting my trial:

    'Sadly, as it has been for some time, the questions I have, have no absolute answers. I, and my fellow ratties, ARE the answer.  But, I asked a few none-the-less.  The one of most importance:
"Having completed anti-PD1, is my immune system permanently changed, or was the change temporary?"
After some discussion and recognition that no one really knows the answer to this...the answer was:
"Yes, it is most likely that your immune system has been altered permanently via your central memory T cells."
     The good news, if this is indeed the case, is that, theoretically, my memory T cells will be around for a good while and continue to kill off any horrid little melanoma cells fluttering about. On the down side, a forever changed immune system could continue to put me at greater risk for immune stimulated disease processes...but what's a girl to do?  And mostly...time will tell all.'

My answer is, "Soooo very changed indeed!"  Given the way immunotherapy works, that is the hope.  But, it is not without issues.  Personally, my difficulties have been minimal compared to what folks have dealt with on and post ipi, and even mild compared to what some ratties have experienced on anti-PD1.   However, events that I am certain are side effects of the treatment I received continue to this day.  The weird thing about them...or more likely, about me!!!...is that I never see them for what they are at the start.  It's kind of like living with an unstable person.  You're just kind-of rolling along, thinking, "Whew, we're doing pretty well here.  Everything seems cool."  When apropos of nothing, the request, "Pass the potatoes, please." has a certain tenor, a tenseness, a harsh screech, hanging, just under the surface.  And you know...  Shit!  Here we go again.

For instance, my last/current tadah~  Got a bit of a cold, nothing terrible, from one of my critters at work.  As per my usual, such a thing flared up my asthma a bit, that's a norm for me for my whole life.  So, no worries.  The nurses ask why I am limping at work.  I reply, "I don't know.  I think I must have twisted my hip funny putting down some mulch for a friend."  An activity that I had participated in just a few days before. Then, I realize,"Man, this cold weather sure has my skin dry and itchy!"  Ok, then, wow, "Did I bite my tongue?  I don't remember doing that.  Wait a minute!!!"  And, sure enough...a peek in the mirror shows lesions all along the side of my tongue, red and angry.  By the next day they are along the other side as well.  The itchy skin is full blown welts in places and all the residual granulomas from my vaccine injections are red, warm and swollen.  The fact that my wheezing has continued, and even worsened, over the past four weeks despite aggressive nebulizations for my asthma...makes me pretty confident that I am dealing with a mild pneumonitis, much like what would happen with some regularity after my anti-PD1 infusions.  Add to that the fact that my joint aches have roamed like the Greek humors from right hip to left ankle, right knee, left wrist and any mixture of the above.  There has been no putting down of mulch.  No strain.  Just me.  Post anti-PD1 with my weird T cells.  My personal theory is that whenever I get a mild viral process, and perhaps sometimes even when I don't, my T cells go a bit nuts and cause various autoimmune problems.  Here is what  more important folks have to say:

Arthritis and Tenosynovitis Associated with the Anti-PD1 Antibody Pembrolizumab in Metastatic Melanoma.  Chan, Kefford, Carlino, et al.  J Immunother.  2014 November 20.

"We report the acute onset of polyarticular inflammatory arthritis in 2 patients receiving the immune check-point inhibitor, pembrolizumab....after 14 and 11 months of therapy, respectively....Good symptomatic control was obtained with bisphosphonates (drugs to prevent bone loss like Boniva and Fosamax) and salazopyrin (Sulphasalazine - an anti-inflammatory), avoiding use of T cell immunosuppressants.  These cases raise important questions on whether anti-PD1 therapy allows preexisting autoimmune  T cell clones to escape tolerance by suppressing regulatory T cells or whether they allow autoimmunity to develop de novo.  These conditions heighten our awareness of complications associate with the use of these agents..."  

So...basically...these folks are noting other patients who have developed joint problems much as I have. Their question is.... Did I (and these peeps) have the propensity, though unrevealed prior to anti-PD1 therapy, for an arthritic process?  OR...did anti-PD1 cause the arthritic process on its own?  As more folks take these drugs, I think more examples of autoimmune problems not only while on anti-PD1, but in the months and years(!!!) afterwards - arthralgias as well as issues related to derm (itching), gastro (mouth ulcers, colitis), pulmonary (wheezing, pneumonitis, strange spots on CXR) - will be noted.  Of course, to be able to sit here kvetching about my little aches and itches 55 months out from Stage IV melanoma and 17 months post a 2 1/2 year trial of Nivo makes me incredibly lucky indeed.

Oh, on a lighter note!!  I'm a good 12 hours into my post-Thanksgiving/pre-New Year's CLEANSE!!!!  Yep!  Decided good ol' Gwennie and other celebs who like to publish the contents of their intestinal tracks (or absence of contents in that area) had the scoop on health and beauty!  Why should I pass up such a good thing?!  NOT!!!!  In an episode of what I am certain was an event similar to those noted above, several months ago, I got a gastro bug that was going around the critters in the office.  A little headache (ok...it did last two weeks), some vomiting and a little diarrhea....turned into 12 hours of profusely bloody diarrhea.  So, B, Tammy B, Weber, and now my gastroenterologist (Yes, Virginia....I am rapidly acquiring EVERY sort of doctor now!!!) have gone into complete panic and melt-down mode (all at different times, thank goodness....SHEW, you people wear a girl out!!!!) and tomorrow at the ever lovin' BUTT CRACK of dawn (6:40am!  W.T.H. people??!!)...and BOY!!!!...it will be BUTT CRACK fo sho!!!...I will be having a colonoscopy.

I'll be lettin' y'all know how that all comes out!!!  I know you can't wait to hear!!!

Salud! - c