I feel like I’m tied to a railroad track, and see the light of the train approaching. And I don’t know if it’s one mile away, or 500.
Anonymous, a patient three years into leukemia remission.
Cancer will give many of us that oncoming train feeling, but of course the light is always there. We’re just good at denial. When we’re young and healthy the train is probably far away. When we’re 93 it’s pretty close. In between we try not to look.
There’s only one “train”, but there are lots of smaller hits along the way. Bicycles and cars maybe. One of them ran into me recently, so I’ve renewed an old interest in the so-called “rheumatic disorders” (misleadingly named after bodily fluid flow).
It really is an old interest. Before I figured out how to do medical school [1], I closely read the 1982 version of the Arthritis Foundation’s “Primer on the Rheumatic Diseases”. Within the broad bounds of unreliable memory I recall that osteoarthritis was a “wear and tear” disorder of aging, rheumatoid arthritis and a handful of other disorders were “auto-immune” diseases, gout and non-gout crystal deposition were relatively well understood, and many viral and non-viral diseases (Gonorrhea and, a bit later, Lyme) caused arthritis. Steroids (not the androgen variety!) worked very well on the auto-immune disorders, but the long term side-effects were horrible and inevitable. We had reasonable drugs for Gout, gold for Rheumatoid arthritis (some value [7]), and nothing for osteoarthritis. Okay, so we had NSAIDs like ibuprofen, but we already suspected they were a mixed blessing. We’ve kind of given up on them.
Things aren’t that much different 33 years later. Relatively recently we’ve realized that “osteoarthritis” covers a multitude of evils, some or all of which, like “psoriatic” arthritis, are more than “wear and tear”. We still don’t have any great treatments for Systemic Lupus Erythematosis, though we now do less harm with the treatments we have. Rheumatoid arthritis has seen the most care improvements, but, amazingly, we can’t actually cure it or any other auto-immune arthritis [3]. We still wonder about the role of infectious agents in creating or sustaining auto-immune disorders but we have few leads [2][6]. The most recent (2005) edition of the Primer on Rheumatic disease says of Osteoarthritis “It is clear that this … includes a variety of different conditions, but we have made less progress …”.
More recent publications have even undone old certainties; we’re no longer confident that the various flavors of psoriatic and osteoarthritis are primarily “arthritic” (greek: Arthron, joint). Disorders along the osteoarthritis - psoriatic arthritis spectrum may begin as diseases of the tendons. Some of them may be lifelong disorders of tissue healing; small injuries accumulate due to a healing defect, perhaps with later onset of an auto-immune component reacting to disordered tissues.
My medical school interest became personal as I watched my mother go through the arthritis experience for about 35 years, ending as “rheumatoid arthritis” (our classifications are imprecise). It wasn’t pretty.
Which is all by way of introducing this “reference post”; a blog post that I’m going to be revising and extending. It’s a post supporting my surveillance of our historically limited knowledge base. I’ll revise it periodically over the next year or two. Sometimes I’ll post/tweet about updates to this reference post, but most of the interesting results will appear in a pinboard RSS stream tagged “arthritis” [4].
My surveillance relies on PubMed [5] (National Library of Medicine) RSS feeds. Anyone can create these, but I’ve never seen anyone but me write about them. I’ll list them by topic below, but first I’ll describe what I’m not monitoring.
I’m not monitoring care guidelines or the cutting edge of rheumatologic practice. I see a rheumatologist for that; that’s his job. If I want an update on current practices I’ll take a look at FP Notebook’s Rheumatology Book. I’m not interested in alternative or complementary therapies — that way lies madness. I’m only mildly curious about lifestyle factors; mostly because we know so little and very little research is going to get funded.
I am curious about tolerance induction — the Holy Grail of the rheumatic disorder treatment. We’ve been hammering on this decades, but we have new tools now. This is what we really want - a cure for at least some of these diseases. I’m looking for articles on disordered healing and secondary arthritic conditions, but I’ve yet to figure out a good search for that one. Likewise I’m looking for articles that relate loss of self-tolerance to a dysfunctional pseudo-neoplastic component of the immune system (yeah, this is definitely fuzzy). More concretely anything about the role of infections organisms in precipitating or maintaining arthritis.
Here are the RSS feeds and “similar articles” queries I’m revising and using for each of these topics. I wish there were RSS feeds for the “similar to” queries, as I learn the topics i’ll put create RSS feeds with similar results.
tolerance induction
- tolerance induction in arthritis (feed)
- peptide based immunotherapy (not limited arthritis, feed)
- T cell immunoglobulin-3 (Tim-3) therapy (query)
- tolerogenic dendritic cells
tendon injury (enthesitis) and arthritis
- psoriatic arthritis - natural history (not a query because this seems to be only article!)
- cimetidine and innate immunity (feed - because of this post)
- fn -
[1] The way to do the didactic portion medical school is to maintain a relentless focus on examinations. If you’re doing well you may then indulge your passion and curiosity.
[2] As a still distractible student I read the first speculative article written on an association between bugs living in the high acid stomach and gastric ulcer disease. Before then we thought the stomach was sterile; nothing could live in such a disagreeable environment. That probably contributed to my extremophiles and auto-immune disease post.
[3] Juvenile Rheumatoid Arthritis does resolve about half the time. Which is curious.
[4] Like all things Pinboard it has an RSS Feed: http://feeds.pinboard.in/rss/secret:c6ea18730310000211dc/u:jgordon/t:arthritis/. Sadly there are no RSS feeds for “similar article” queries and “My NCBI” doesn’t show feeds.
[5] My medical informatics career began in Family Medicine residence as a beta tester of the “Grateful Med” software. I believe the product manager, Rose Marie Woodsmall, was a dead head. I was among the last generation of medical students to use the paper Index Medicus to do journal research.
[6] I’d wondered years ago why we weren’t mining synovial fluid for foreign DNA. Turns out this was done in 2001 with interesting results, but the follow-up was limited until “microbiome” became a funding source.
[7] Gold was used to treat Rheumatoid arthritis from at least 1945 through the early 1990s. I seem to remember it was sometimes associated with extended remissions. I can find almost nothing on it written after 1965 or so, and nothing at all on how it worked. There’s very little on long term outcomes. Which is, you know, profoundly weird.
Update 12/18/2015
I have a hunch that whatever is afflicting me now is the end-stage of a congenital defect with soft tissue/tendon formation. I’ve always been prone to calcium deposits along tendons and to overuse tendonopathies. It would not be surprising that as I’ve aged my body’s ability to manage this problem, and heal from injury, has declined. That in turn could lead to some secondary auto-immune issues (prolonged inflammatory/antigen spill issues). I haven’t come up with a search criteria yet to explore this idea; it would probably show up in whole genome analyses. I would need to look for discovery of a gene associated with auto-immune arthritis/osteoarthritis that was important for tendon formation.
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