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[Dr. Handy] Hi, welcome to Harrison's Podclass, where we discuss important concepts in internal medicine. I'm Cathy Handy. [Dr. Wiener] And I'm Charlie Wiener and we're coming to you from the Johns Hopkins School of Medicine. Okay, welcome to episode 58, a 65-year-old with joint pain. - Hi Cathy. - [Dr. Handy] Hey Charlie.
[Dr. Wiener] Okay, well today's case is a 65-year-old woman with a 10-year history of untreated rheumatoid arthritis who presents to your clinic with worsening joint pain and malaise over the last six months. On examination of her joints, she has swan neck deformities in all her deviations. Let's stop there and talk a little bit about rheumatoid arthritis.
[Dr. Handy] Okay, so in rheumatoid arthritis, the most common joints that you would see involved would be the wrist, the metacarpophalangeal joints, and the proximal interphalangeal joints. Distal interphalangeal joint involvement is rarely due to rheumatoid arthritis and more often due to coexisting osteoarthritis.
Swan neck deformity, like you mentioned in this case, refers to the hyperextension of the PIP joint with flexion of the DIP joint, which is most commonly seen in rheumatoid arthritis. [Dr. Wiener] As part of the initial evaluation, oftentimes we obtain plain radiographs in patients with suspected RA. Plain radiographs are readily available and they allow easy film comparison. What would you expect radiographically early and late in the presentation of RA?
Note, this woman supposedly has not had treatment for 10 years. [Dr. Handy] The earliest radiologic sign of RA is juxta-articular osteopenia, although this may be difficult to appreciate on some of the newer digitized films. Other findings that you would see include soft tissue swelling, symmetric joint space loss, and subchondral erosions most frequently in the wrist, the metacarpophalangeal and the proximal interphalangeal joints and metatarsophalangeal joints.
[Dr. Wiener] Okay, so radiology is still useful in this diagnosis it sounds like. [Dr. Handy] Mmhmm. [Dr. Wiener] Okay, well let's get back to this patient. Her skin examination demonstrates rheumatoid nodules in the olecranon bursa bilaterally, and notably on abdominal examination, you palpate her spleen, she clearly has splenomegaly. [Dr. Handy] Splenomegaly in someone with nodular rheumatoid arthritis, like you mentioned, should make you think of Felty's syndrome.
[Dr. Wiener] Well, I'll give you some lab studies. How about that? [Dr. Handy] That would be helpful. [Dr. Wiener] Well, her laboratory studies show neutropenia, an elevated C-reactive protein and anemia. And as you predicted, she's diagnosed with Felty's syndrome. So tell me more about that.
[Dr. Handy] Felty's syndrome is a clinical diagnosis and it's defined by the clinical triad of neutropenia, which you mentioned on her labs, splenomegaly, which we noted on physical exam, and nodular rheumatoid arthritis. It's seen in less than 1% of patients, though, so it's quite rare, and its incidence appears to be declining in the face of more aggressive treatment of the joint disease, as it typically occurs really in late stages of severe rheumatoid arthritis.
[Dr. Wiener] So it sounds like this lady is a setup for that. [Dr. Handy] Right, exactly. [Dr. Wiener] So the question is going to ask us, what type of hematologic malignancy or lymphoproliferative disorder may present similarly to Felty's syndrome in patients with rheumatoid arthritis? And the options are A. acute myeloid leukemia; B. chronic lymphocytic leukemia; C. essential thrombocytosis; D. polycythemia vera; or option E. a T-cell large granular lymphocyte leukemia.
[Dr. Handy] Of the diseases listed, T-cell large granular lymphocyte leukemia, or T-LGL for short because that's also easier to say, may have a similar clinical presentation and it often occurs in association with RA. [Dr. Wiener] Wow. Tell me about T-LGL. [Dr. Handy] So it's characterized by a chronic indolent clonal growth of LGL cells, and that leads to neutropenia and splenomegaly. As opposed to Felty's syndrome, T-LGL may develop early in the course of rheumatoid arthritis.
Leukopenia apart from these disorders is uncommon and occurs more commonly as a side effect of drug therapy. [Dr. Wiener] Okay. So what about the other answers then? [Dr. Handy] Splenomegaly can be seen in any of the malignancies listed, although probably less common in AML compared to the others. Neutropenia is not as common in essential thrombocytosis and polycythemia vera.
Additionally, AML, CLL, essential thrombocytosis, and polycythemia vera are not seen more frequently in patients with RA compared to the general population. [Dr. Wiener] What about lymphoma though? [Dr. Handy] Lymphoma is increased in patients with RA, but is not typically similar to Felty's syndrome in terms of its clinical presentation. The most common type of lymphoma diagnosed in patients with RA is diffuse large B-cell lymphoma.
[Dr. Wiener] Okay. You mentioned that Felty's syndrome is pretty rare, so let's get back to a more general question about rheumatoid arthritis. The question asks, patients with rheumatoid arthritis are at higher risk for all of the following health conditions than the general population, except? So options are A. colorectal cancer; B. coronary artery disease; C. hypoandrogenism; D. lymphoma; and E. osteoporosis.
[Dr. Handy] The most common cause of death in patients with RA is cardiovascular disease. The incidence of coronary artery disease and carotid atherosclerosis is higher in RA patients than in the general population, even when you control for traditional cardiac risk factors like hypertension, obesity, high cholesterol, diabetes and cigarette smoking. [Dr. Wiener] And you already mentioned that the risk of lymphoma is increased in RA patients.
[Dr. Handy] Yeah, large cohort studies have shown a two to four-fold increased risk of lymphoma in RA patients compared with the general population. And like I mentioned before, the most common histopathologic sight that you would get is a diffuse large B-cell lymphoma. [Dr. Wiener] What about the other answers then?
[Dr. Handy] Well, with regards to cancer, which as you know is my favorite topic, RA has not been associated with increased rates of colorectal cancer or other solid tumors with the exception of lung cancer, which is slightly increased. [Dr. Wiener] Okay. So the answer is A. rheumatoid arthritis is not associated with an increased risk of colon cancer. [Dr. Handy] That's right.
So just to go through the other answers, osteoporosis is more common in patients with RA than age and sex-matched population controls, and the prevalence is about 20-30% in RA patients. We think that the inflammatory millieu of the joint probably spills over into the rest of the body and promotes generalized bone loss by activating osteoclasts. Chronic use of glucocorticoids and disability-related immobility probably also contributes to osteoporosis.
With regards to option C and hypoandrogenism, men and post-menopausal women with RA do have lower mean serum testosterone levels, luteinizing hormone, or LH levels, and DHEA levels compared to control populations. It has thus been hypothesized that hypoandrogenism may play a role in the pathogenesis of RA or arise as a consequence of the chronic inflammatory response.
[Dr. Wiener] Okay. So the teaching point here is that rheumatoid arthritis plus splenomegaly plus neutropenia is defined as Felty's syndrome, which may have a similar presentation to the T-cell LGL, which also occurs in association with rheumatoid arthritis.
Cardiovascular disease, like the general population, is the most common cause of death in RA patients, and RA patients are at higher risk of a host of other disorders, but appear at this point to not be at increased risk of many solid tumors, such as colon cancer. [Dr. Handy] And if you want to learn more about this, you can check out Harrison's chapter on rheumatoid arthritis. [outro music] [Mr. Shanahan] This is Jim Shanahan, publisher at McGraw Hill.
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