AIMSS: How Aromatase Inhibitors Can Affect Hands and Wrists

Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here’s your host, Breastcancer.org Senior Editor, Jamie DePolo.

Jamie DePolo: Hello, as always, thanks for listening. Bone and joint pain are some of the most common side effects of aromatase inhibitors, which are medicines for hormone receptor-positive breast cancer. The official name for this is aromatase inhibitor associated, or sometimes induced, musculoskeletal syndrome, also called AIMSS. Many people report pain in the knees, ankles, and hips, but the hands and the wrists also could be affected.

I'm joined by Dr. David Bozentka, professor of orthopedic surgery at the Hospital of the University of Pennsylvania, who also serves as chief of hand surgery and chief of orthopedic surgery at Penn Presbyterian Medical Center. Dr. Bozentka is going to help us understand how AIMSS can affect the wrists and hands, including lesser known symptoms such as carpal tunnel syndrome, trigger finger, and tendonitis.

Dr. Bozentka, welcome to the podcast.

Dr. David Bozentka: Thanks for having me on the podcast. It’s a pleasure to be here.

Jamie DePolo: So, do we know why aromatase inhibitors can cause this level of bone and joint pain? I mean, I've talked to various people and they say, oh, you know, it’s really crazy how much my joints hurt.

Dr. David Bozentka: Well, there are several theories. First, you're exactly correct. The aromatase inhibitor musculoskeletal syndrome is a constellation of symptoms, joint pain, swelling, muscle pain. Patients can develop tendonitis, tendon tears, and even carpal tunnel syndrome. The symptoms typically develop within about two months of starting the medication but have been reported even as late as 10 months. Again, there are several theories.

One theory is that the pain may be related to the rapid decrease in estrogen concentration that’s induced by the aromatase inhibitors. Estrogen has what we would say anti-nociceptor properties. So, estrogen decreases pain by acting on certain specific parts of the nervous system. Estrogen can turn down the volume of pain signals traveling to the brain. And so, aromatase inhibitors decrease estrogen levels and these decreased estrogen levels may lead to an increase in the painful stimuli to the brain.

Another theory is that the decreased estrogen results in increased production of what we call pro-inflammatory cytokines in the articular cartilage. The pro-inflammatory cytokines are proteins made by our body’s immune cells that help us start and control inflammation when there’s an injury or infection. You’ve heard probably of interleukin-1, interleukin-6, or tumor necrosis factor. If they stay active for too long, they can cause problems like swelling, pain, and even damage to healthy tissues.

And finally, there is some evidence that the tendonitis that occurs may be related to the decreased estrogen since we know there are changes to tendons, the tendon sheaths, and even the covering of the tendon we call tenosynovium, with changes in estrogen. MRI studies and ultrasound have shown fluid accumulation around these structures that can lead to problems like carpal tunnel syndrome, trigger finger, and De Quervain’s tendonitis.

Jamie DePolo: Okay. So, it could be a number of factors going on. Now, are there factors that could put somebody at higher risk for this, for AIMSS? Like, I don’t know if there are other diseases, like other inflammatory diseases, like lupus or some sort of other autoimmune disorders. Would that put somebody at a higher risk for the syndrome?

Dr. David Bozentka: Well, there are a number of studies that looked at the various risk factors, but many of them have inconsistent findings. Some studies have shown there may be an association with an elevated BMI. So, patients that may be overweight may have an increased incidence. While other studies have not shown that association. Some studies are showing that younger patients, particularly younger than 60, or patients in peri-menopause compared to older patients, may develop symptoms. And this may be related to a greater drop in estrogen levels in those patients that lead up to menopause compared to patients that have already been into menopause for a longer period of time because of those estrogen changes.

There are some studies that show that other factors, like prior musculoskeletal-related symptoms, prior chemotherapy, or hormone therapy before cancer treatment may increase your risk. And there are certain genetic predispositions that may be associated, but there are several factors that are considered.

Jamie DePolo: Okay. Would arthritis put somebody at a higher risk? I mean, that’s already having swelling in the joints or does that not really matter, or don’t we know?

Dr. David Bozentka: We don’t know, but…

Jamie DePolo: Okay.

Dr. David Bozentka: …having arthritis does increase the likelihood of you having aggravation of that arthritic process, and so it would make sense that there would be increased likelihood of having symptoms when you start these aromatase inhibitors.

Jamie DePolo: Okay. Well, and if we don’t really know all the causes or the risk factors, it sounds like, then there’s probably not a lot that somebody could do to reduce that risk because it doesn’t sound like anything’s hard and fast and known yet.

Dr. David Bozentka: Well, there’s certain considerations of things that you may be able to do to help decrease that risk. There are some studies that show exercise can be helpful. We do know that exercise decreases the pain associated with these issues. Early diagnosis. If you have an early diagnosis of carpal tunnel syndrome or some of the tendonitis type of issues, will decrease the chance of this type of process progressing. And so, I guess if we can catch the symptoms earlier, we could reduce the chance of these issues progressing.

Jamie DePolo: Okay. Now, based on some of the comments in our virtual support groups, it sounds like a lot of people weren’t really aware that the aromatase inhibitors could cause problems like carpal tunnel syndrome or trigger finger or tendonitis in the hands. They were thinking more hips, knees, ankles, feet. In your experience, how common is it for the hands and the wrists to be affected by aromatase inhibitors?

Dr. David Bozentka: Well, it’s interesting, there are several studies that show a very high incidence. There are studies that show up to 50% of patients that take these medications will have symptoms. But most of the larger studies have shown a relatively limited number. So, there’s a large population study that showed carpal tunnel syndrome developed in 1.3% of patients taking these medications compared to 0.4% of patients that were not taking the medications. We do know that carpal tunnel, trigger fingers, and tendonitis is a well-recognized complication of the medications and it has been reported that it occurs even 10 times more than patients that are taking tamoxifen.

Jamie DePolo: Interesting. And I wonder, too, if it’s because maybe somebody isn’t really associating the aromatase inhibitor with the carpal tunnel syndrome. You know, maybe they’re still working while they’re taking the medicine and maybe they type a lot all day and so they’re linking the carpal tunnel to, like employment or something else that they’re doing and they’re not thinking that it’s coming from the AI. Have you seen that at all?

Dr. David Bozentka: I would agree. No question. Patients quite often will come in that have had months of symptoms that they’ve just been putting off thinking that it will go away and just don’t correlate it with the medications they’re taking.

Jamie DePolo: Okay. So, let’s talk about ways to manage and treat these hand and wrist things. Why don’t we start with carpal tunnel syndrome? So, what do you recommend to people if they come in, they’re taking an AI, and they’ve got carpal tunnel syndrome? What can be done?

Dr. David Bozentka: So, first of all we need to know, what’s the diagnosis? What is carpal tunnel syndrome? Because many patients will come in just with hand pain and believe they have carpal tunnel syndrome.

Jamie DePolo: Okay.

Dr. David Bozentka: Carpal tunnel syndrome is a nerve compression of the median nerve at your wrist. And so, pressure around the wrist will tend to manifest as numbness and tingling. Patients will notice numbness and tingling in their hand, particularly in their thumb, index, long, and half the ring finger. They’ll awaken at night, have to shake their hand to try to get rid of it. They’ll have symptoms when they’re driving a car or reading a book. Usually, the diagnosis is made by history and physical examination by a healthcare provider. But there are situations where we need to obtain an EMG to help confirm the diagnosis.

Jamie DePolo: And I'm sorry, what’s an EMG?

Dr. David Bozentka: An EMG is an electromyogram. They stimulate the nerve in an area and have certain types of probes on your fingers, and they see how quickly the nerve conducts electricity. If there’s slowing in a certain area because there’s compression of a nerve that helps confirm the diagnosis. So, it helps to confirm the diagnosis and determine severity.

Jamie DePolo: Okay. Okay.

Dr. David Bozentka: Once you have the diagnosis, the first step of treatment is typically using a wrist splint. The wrist splint holds your wrist in the neutral position, halfway between fully flexed and fully extended, because we know that that holds the wrist in the optimal alignment to decrease pressure on the nerve. When you fully bend your wrist or pull your wrist back, the tunnel that that nerve runs through gets smaller. So, we need to hold the wrist in that position. We use it at night. If there’s certain activities during the day that bring on the symptoms, we will put it on during the day as well. 

We can use anti-inflammatories to help with the pain. If the symptoms persist despite a splint, an injection can provide some temporary improvement. And then if the symptoms progress or become very bothersome, there’s a relatively minor procedure that we can do to take the pressure off the nerve. It’s called a carpal tunnel release.

Jamie DePolo: Okay. And what does that involve?

Dr. David Bozentka: It’s an outpatient surgical procedure that can be performed under local [anesthesia] and some patients would like to have some IV sedation. It takes about 10 or 15 minutes and basically cuts the ligament that’s over the top of the nerve and the ligament heals in a lengthened position so there’s less pressure on the nerve. Patients are in a dressing for about a week. They do have to take care of the area for several weeks until the wound is healed and then they progress. It is a procedure that typically takes the pressure off the nerve, particularly if you catch the process early on in the mild to moderate stages. As it progresses into the more severe stages, you may not get quite as much relief as you would early on.

Jamie DePolo: Okay. And then, what about trigger finger? How is that treated?

Dr. David Bozentka: A trigger finger is a tendonitis we call stenosing flexor tenosynovitis. Patients will have locking or triggering of their finger. They’ll say, when they make a fist, the finger gets stuck.

Jamie DePolo: Okay.

Dr. David Bozentka: And it just takes more force to straighten their finger. The tendons that let you bend your fingers run through a sheath and that sheath holds the tendons close to the bone. Over time, we believe that sheath becomes thickened, which leads to a lump on the tendon. So, as the muscles in your forearm contract to pull your fingers down this lump gets pulled outside the sheath and gets stuck because of the discrepancy in size between the tendon and the sheath, and it causes that extra force to straighten your finger out that causes that locking sensation. It’s a very common problem. It can be associated with other medical problems like diabetes and other issues. In most cases, I tell patients, if you have to have a hand problem, trigger finger is the one that you want. It’s just really treated in a very straightforward manner.

Jamie DePolo: Okay. And so, what do you do to treat it?

Dr. David Bozentka: In the early stages, we can use a splint. About 60% of the time, we can cure trigger finger with a steroid injection. If it continues, there’s a very minor procedure, even more minor than a carpal tunnel release, where we cut a tight ligament that’s over the top of the tendon and that usually takes care of it. The main issue with the procedure on the palm side of your hand is the scar is uncomfortable for a couple of months. But typically, that takes care of the triggering.

Jamie DePolo: Okay. And trigger finger, help me to understand because I haven’t had it and I haven’t really talked to anybody who had it. Is it painful when the finger gets stuck or is it just annoying?

Dr. David Bozentka: A combination of both. There’s some folks that will come in and say, it is very, very painful. Even without the triggering, just at the very early stages when they have the tendonitis. And that pain usually occurs on the palm side of your hand at the base of your finger and it’s usually increased with activities. There are some people that will say that the locking has no discomfort, but just is more of an annoyance because every time they make a fist, they have to use their other hand to open the finger in order to straighten it out.

Jamie DePolo: Sure. Sure. That makes sense. Okay. Now, that trigger finger to me, and I could be wrong, I am not the expert, sounds like a specific kind of tendonitis, but then there’s sort of general tendonitis in the hands and wrists that can be caused by AIs.

Dr. David Bozentka: Any tendon can be involved and there are multiple tendons in your wrist, hand, and forearm. So, what’s most important is if you can localize your symptoms. Are they on the palm side, or the thumb side, or on the small finger side of the wrist or hand? Because when you can localize it, that helps us focus our treatment options on that area.

So, yes, any tendon could be involved. One of the most common types of tendonitis in the wrist is what’s called De Quervain’s tendonitis. It’s tendonitis right at the base of the thumb where patients will develop a lifting, grasping. It is relatively localized just at the forearm area, just proximal just toward the arm side of your thumb. It’s a problem that occurs on a common basis either injury, overuse. It can occur with aromatase inhibitors as well. And in a very similar manner, we’ll use a splint, medications, injections often cure it, and occasionally we do surgery release for that as well. But it’s helpful to be able to localize your symptoms. It’s most beneficial for the healthcare provider that you see.

Jamie DePolo: Okay. So, basically kind of figure out where in the hand it is and maybe how you move makes it worse. Is that helpful to know as well?

Dr. David Bozentka: Absolutely. What are the alleviating factors? What are the aggravating factors? When does it occur? How often does it occur? It will help us determine diagnosis and recommendations for treatment. 

Jamie DePolo: Okay. Okay. Well, thank you. That’s all been very helpful. I have one final question. If somebody is just starting an aromatase inhibitor…you mentioned earlier, that treating these symptoms earlier or diagnosing and treating the symptoms early is very helpful. So, would you have any advice for somebody who, say, is scheduled to start an aromatase inhibitor tomorrow? What would you tell them to do or to think about?

Dr. David Bozentka: Well, I think it is important even before you start the medication to understand the potential issues, the potential symptoms. So, if you start to develop joint pain, stiffness, numbness or tingling, difficulty moving your fingers while you're taking the medication, particularly early on, identify a healthcare provider to help address this. And as I said, early treatment tends to lead to better results.

Jamie DePolo: Okay. Excellent. And would you say, is it better, like would you start with your GP or is it better to seek out a hand specialist to start with or does it matter?

Dr. David Bozentka: I always like to go to the GP first. They’re your quarterback. They help guide the process. So, early on if you may have numbness and tingling, they may say try the splint and then guide you to the hand care specialist that you should see. If things are not improving then, of course, you take the next route and get further assessment.

Jamie DePolo: Okay. Perfect. Dr. Bozentka, thank you so much. This has been very helpful. I appreciate all your insights and thank you for your time.

Dr. David Bozentka: Well, thank you for having me.

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