QD Clinic: RA, IBD and Frank's sign Save

Welcome to Obesity QD Clinic. I'm Derek Mueller, PA from St. Clair Shores of Michigan. And today my case is entitled rheumatoid arthritis, IBD, and Frank sign — Frank Sinatra, Uncle Frank from Home Alone? You'll find out.

So this case is about a patient of mine, a 71-year-old male with rheumatoid factor CCP-positive rheumatoid arthritis and ulcerative colitis that were diagnosed about two years prior. And the gentleman is currently well managed on a combination of infliximab and sulfasalazine. He has a couple of harrowing comorbidities including obesity with a BMI of 37, coronary artery disease, aortic root dilation, hyperlipidemia, hypertension, bilateral advanced knee osteoarthritis, and lumbar degenerative disc disease.

At this time his rheumatoid arthritis and ulcerative colitis are well managed and some of his major issues are more so related to degenerative and mechanical musculoskeletal disease. His most recent exam, he only had two tender joints, both of his knees, and he had a high-sensitivity CRP that was technically elevated at five milligrams per liter.

So really since his RA and ulcerative colitis were under good control, I kind of opened the floor to him about what were his major concerns, and his big concern after multiple visits of discussing the cardiovascular risk associated with inflammatory disease was really his cardiovascular risk. He said, "I want to focus on doing what I can do to prevent heart disease and prevent anything that's going to shorten my lifespan." So that opened up the floor to some interesting conversations.

And one thing that I didn't note physically on his exam — something that I had not noted the first time that I saw this gentleman — was he had a very distinctive crease on his earlobe in a diagonal pattern. So this is known as the diagonal earlobe crease sign, also known as Frank sign.

If this is not something you're familiar with, or if you've heard it and it's kind of something you may have forgotten about, we're just going to go over some history and the significance of what the heck is Frank sign, or a diagonal earlobe crease, and why do I care about it in my patients.

So in 1973, an American pulmonologist named Dr. Sanders T. Frank wrote a short letter in the New England Journal of Medicine that he'd noticed that some of his patients who had this diagonal earlobe crease seemed to be associated with coronary artery disease. And fun fact about this doctor — he also published on the pulmonary manifestations of rheumatoid arthritis. So a well-versed guy.

This was an observation in the 1970s, but how has this panned out now in the modern era? Well, actually the link is quite strong. According to a 2025 systematic meta-analysis from the Journal of Laryngology and Otology, people who have this crease sign did have a four times higher likelihood of having coronary artery disease. And this actually holds up independent of age and other risk factors. It's also been shown that bilaterality of these creases may confer a higher coronary artery disease risk than one crease alone, and also potentially the depth — really how profound these creases are — there may be a larger burden of atherosclerotic heart disease. And it's also a predictor of future events. A longitudinal population-based study, the Copenhagen City Heart Study, followed 11,000 people for over 35 years and found that the earlobe crease sign independently predicted heart attacks, ischemic heart disease, strokes, carotid plaques, and even cerebral small vessel disease.

But here's really the big-time caveat with this fancy sign — even though there is an association, as a standalone diagnostic test it performs lousy. The sensitivities and specificities are all over the map, sensitivities ranging from 26 to 90%, specificities of 32 to 96%. So it really on its own does not shift the probability of disease one way or the other. And there's also not really a standardized way to grade earlobe creases. So if it's observed, it should prompt the possibility of a cardiovascular workup or looking at other factors, not relying on it on its own. And also, interestingly, this is not incorporated into any kind of cardiovascular risk calculator. So take it with a grain of salt.

And why does this even happen anyway? What's the deal with this? The truth is nobody really knows. A few leading theories are perhaps this is a sign of small vessel vasculopathy, since the earlobes are an end-artery blood supply that may be an early warning site of cardiovascular disease. And there are also theories of endothelial dysfunction that lead to this physical finding. And then maybe this is also a result of accelerated biological aging. So really at best it's a
it's a free uh visible marker that could suggest the possibility of coronary artery disease. Um it's not a diagnostic test. So um just uh uh understand the limitations of that finding.

Uh so with our patient who had bilateral quite deep uh diagonal earlobe crease signs or Frank's signs, we talked about starting a GLP-1 agonist drug to um manage his obesity and cardiovascular risk. Uh and thankfully he was able to access this through the Medicare Bridge program and he is uh successfully tolerating the drug. So uh we're waiting to see um how he responds and what his uh hopefully his long-term risk reduction will be.

Uh so that's it for me. Thank you again for listening and keep an eye out for more content just like this all month for RheumNow's Obesity Campaign.