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Polyarticular Diseases

When someone comes in and says, "I got arthritis and my joints hurt." The real differential diagnosis is one of three general types of disease groups. First of all, you could have a true inflammatory synovitis or a polyarthritis. Arthritis means, effectively, synovitis for almost all practical purposes. So no synovial inflammation, no "_itis". Or you can have multiple structural lesions which are degenerative joint diseases or, most commonly, you can have a process that is not in the joint but is outside of the joint. The vast number of differential difficulties that we have as rheumatologists is to separate number 1 from number 3 – what is truly articular disease that is inflammatory and what is periarticular disease.

Now, what do you want to really know on the history? What I want to know from the history is is the process inflammatory or non-inflammatory. That’s the major thing I learn from the history and so I want to know what happens to the pain primarily when the people rest and then use it versus what happens as they keep exercising. In general, with inflammatory diseases, people’s

The second test is the rheumatoid factor. You all know about the rheumatoid factor but I want to emphasize just several points. First of all, a rheumatoid factor is a true autoantibody. It is a self antibody against self antibodies and it is associated with many things but the frequency of association does change from disease to disease.

We all think of it as a rheumatoid arthritis test but we have to remember two things. First of all, only 80% of patients with real RA have a positive rheumatoid factor. So if someone comes in, they act, smell and look like rheumatoid arthritis but the rheumatoid factor is negative, they still have RA. The second point is every other chronic inflammatory infectious disease also has a certain percentage of positive rheumatoid factor frequencies that vary from 10-20% to 50% depending on the disease process and usually is low titer.

So the bottom line is if someone comes in with aches and pains and has a low titer rheumatoid factor, if clinically you can’t make the diagnosis of RA, you throw the rheumatoid factor away. Likewise, remember that as patients get older, their "normal" value of rheumatoid factor goes up. In general, I double the normal rheumatoid factor level – the upper limit of normal – before I get too concerned about it. So if your levels are 20-25 international units (which many labs have) I don’t get too concerned about a rheumatoid factor until it gets about 40 because age, chronic inflammation, all these other diseases can often give you one in that lower range.

What about ANAs? The ANA is the classic rheumatoid test. It is antibodies against nuclear and cytoplasmic antigens and the

Antiphospholipid syndrome and the summary thing that I want you to take home from this is the antiphospholipid syndrome is a fairly vague disease entity that is usually characterized by recurrent fetal loss, thrombocytopenia and/or venous and arterial

The other thing that you have to know about is the fact these antibodies are seen, for example, in 15% of normal females who have had one miscarriage in the first trimester. That’s well-known. The question is what does this mean diagnostically because the number of women who have a miscarriage in the first trimester or they’re first pregnant is fairly high also. So it is unclear, to me anyway, whether you’ve had only one or two miscarriages and you have a positive antiphospholipid antibody whether this means that you "have a disease" or whether that’s just the way God made it at that particular time.

The thing I would like you to take home is be cautious in making the diagnosis of anticardiolipin syndrome only in the setting of recurrent fetal loss and, if in fact you have thromboembolic events in a setting of anticardiolipid syndrome, this mandates lifelong anticoagulation. I think those are two practical points at the present time on antiphospholipid syndrome.

ANCA. The ANCA test is the anti-neutrophilic cytoplasmic antibody. There are two kinds of ANCA – P_ANCA and C-ANCA. This simply means there is an antibody that recognizes the cytoplasm of neutrophils and it recognizes it in two patterns. The thing I think it’s important for you to understand now is C-ANCA is associated with Wagner’s (a very, very high correlation) and P-ANCA is associated with vague, strange vasculitides.

When I talk to the residents, I always ask them "What is a P-ANCA?" and I have a slide that I left out because I offended some people by it. The question is what is a P-ANCA? The people who knew what that was were by definition put on Medicare. So the thing you have to know is not all ANCAs are the same. So if someone comes in and you have a question "Is this Wagner’s or is it not?" And it’s P-ANCA, P-ANCA is a different test essentially than the C-ANCA test is.

Complement and immune complex tests. The bottom line is you can measure complements, you can measure immune complexes. They usually don’t help you much in a given patient at one point in time so yes, if you have active lupus these things change. Yes, if you have this they change but unless you are following them serially, you don’t know what one point in time 

Crystalline arthropathy and infectious arthropathy that you know about is listed and, again, just to reemphasize that 10-15% of the patients with gout present as polyarticular disease.

Someone comes in now with more distended deformity, involvement of the PIPs and MCPs, marked synovitis, nodules on the extensor surfaces, I would be suspicious, could this be gout and could I be stupid? But in general this is RA. This is what RA that’s been going on untreated for awhile looks like.

Sometimes it doesn’t take a rocket scientist to figure this out, to get an x-ray and show flowing syndesmophytes. This is the classic finding of bamboo spine or ankylosing spondylitis but more often someone will come in with one or two joints markedly involved and so the question is, "Well, what is this?" Again, if this asymptomatic, two joints being involved, the differential diagnosis of this would be either Box 3 disease or gout – Box 4 disease. So here’s a situation of actually someone who has gout 

The seronegative spondyloarthropathies present in what I call the five rednesses. I love Oriental food and when you go in a new restaurant they usually have four happinesses or five honeymoons or something and from my memory, since I come from Kansas, we have to be very simple and so I call this the rednesses. So when people have red joints, red eyes – either uveitis or conjunctivitis, red urethra and red posterior or inflammatory bowel disease, then you should think about seronegative spondyloarthropathies. The key to this group is the eyeballs. In many patients with seronegative spondyloarthropathies will have inflammatory symptoms in their eyes, either conjunctivitis or uveitis.

Malar rash. One point about malar rash is, we talk a lot about them, they are not specific for anything. They are only seen in 15-20% of lupus patients and they are seen in every other known thing I’ve ever read about. So it’s a cute thing we talk about, it’s cool to make pictures of but it doesn’t really have much diagnostic specificity. Rashes themselves do but malar rash in and of itself doesn’t mean a whole lot.

This just shows you an aphthous-like ulceration. Again, look in the mouth and ask about aphthous-type ulcerations because they This is an example of scleroderma. Again, patients come in complaining of arthritis, but when you look at them, obviously it’s the scleroderma that is the key point.

Raynaud’s phenomenon. Nonspecific findings seen in every disease known to mankind. One of the things you should always remember is everybody with idiopathic scleroderma has Raynaud’s syndrome. So if someone comes in and has sclerodermatous changes in their hands, particularly if it’s limited, and they don’t have Raynaud’s, look for secondary forms of scleroderma – the various drug exposures, vibrations, all that kind of strange stuff. If someone comes down and you wonder if they’ve got scleroderma, if they don’t have Raynaud’s then you’ve got to really work hard to make that diagnosis. But it’s not specific. It’s seen in all rheumatic diseases.

Remember, patients with rheumatic diseases can get secondary vasculitis so vasculitis is seen in lupus, RA and all these things in addition to the true vasculitides that we talked about.

One of the things that can be helpful is patients who have polymyositis and scleroderma, more prominent polymyositis or have periungual telangiectasias. So I always look at the nails very carefully for two things. If you see pitting, that almost always suggests psoriasis or some other bizarre reaction. If you see telangiectasias, really think about polymyositis. So just looking at the nails sometimes can be very helpful.

Dermatomyositis with muscle atrophy and weakness. These are called Gottron’s. This is Gottron’s sign. What this is is scaly stuff over their knuckles. This is almost always seen in polymyositis. So when you see this, don’t mistake this for arthritis. There is no synovial proliferation there. It’s a funny, scaly skinny rash.

Involvement of urethra, again, makes you think of Box 3 diseases and involvement in the eyes in an inflammatory sense makes you think of Box 3 diseases.

Funny rashes. This is keratoderma blennorrhagicum which is seen in Reiter’s syndrome but essentially is psoriasis of the foot. Again, funny skin rashes that are psoriatic-like in nature make you think of Box 3 diseases. Arthritis in the setting of inflammatory bowel disease should make you think of a causative association at that point.