Is unilateral arm and breast swelling a concern?

[ArtistLike]

I am a 42 year-old male with a mysterious health condition that makes it difficult to sort out the cause of various symptoms, and whether they are definitely caused by it or if they might be caused by something else. I have not been diagnosed with any kind of cancer; I am posting this here to try to figure out if I should have any concern about lymphatic system involvement and, if so, what sort of medical care I should pursue. Details follow.

I have an allergic condition called mast cell activation syndrome (MCAS) that requires me to take relatively high doses of H1- and H2-blocker antihistamines daily. I took ranitidine for several years, until it was recalled by the FDA for being potentially carcinogenic. I replaced it with cimetidine and took that from November 2019 until May 2020, when I became suddenly aware that I have developed gynecomastia, most prominently in my left breast. After consulting with my doctor, she believed that the drug likely induced the breast swelling, but she also noted that my left arm is swollen and larger in circumference than my right arm.

She referred me for a mammogram to be safe, and the doctor there told me that I have bilateral gynecomastia, although it's much more pronounced in the left breast. She saw no signs of cancer-related concerns.

Because I also sometimes have severe pain in my left arm, shoulder, neck, jaw and chest, my doctor also referred me to a cardiovascular specialist. After various tests, she determined that I am in good cardiovascular health; however, she suggested that the swelling on my left side could be associated with a lymph blockage of some kind.

I've been off the cimetidine for about six months now and the swelling has not improved at all. I've read that cimetidine-induced gynecomastia often self-resolves within 6-12 months of discontinuing the drug.

MCAS is a complicated and confusing disorder and it's difficult to know when it is causing problems or if something else may be at play. Two different times, while I was exercising on an elliptical machine, after I broke out in hives, my left arm swelled up suddenly like a balloon--an anaphylactic reaction. I wondered that time why this would happen only in the left arm. Every time I become more active, I get strange, consistent symptoms on my left side, including nerve-type pain, swelling of the left arm, a feeling of fullness and tinnitus in my left ear, and sometimes dull pain in the left breast. I've gone on several long walks of six to eight miles over the past week and now these symptoms are beginning again--tinnitus in my left ear, a feeling of fullness in the ear, dull pain in my neck, jaw and shoulder, and dull aching on and off in my left breast tissue. Since I had already wondered about the possibility of a lymph problem and my cardiologist suggested this, but was unable to recommend how to investigate that, I'm curious whether anyone has any insights into whether this sounds like it could be a lymph problem and, if so, what sort of specialist I might consult.

I am posting this in the lymphoma channel just in case specialists who deal with the lymph system may have some idea of whether or not this sounds like it could involve the lymph. I apologize if this is an inappropriate message to post in a cancer-related channel. I'm just seeking some sort of resolution and appreciate any insights anyone can offer. Thank you.

[Ken_PA]

"My cardiologist felt strongly that the pain on my left side, but not the swelling, is nerve related."
That's not their field, and anyway it doesn't fit.
"What throws me and concerns me is the swelling in the same areas. It seems like a really odd coincidence."
Yes, you are correct. If the swelling and pain occur together and then go away together, in place and time, then the sudden onset pain is not at all likely due to that (excess bone growth pressing on a nerve root which exits the spine). Still, overall inflammation can influence that effect - more below on that.

"cervical spondylosis"
That's outdated, from 7 yrs ago, in an evolving field. You had onset at a young age, so that together with your MCAS tends way more toward inflammatory origin than to 'wear and tear'.

You would more properly be put under SpondyloArthritis (SpA), which is inflammatory. That also gets back to Occam's Razor.

There is a test for 'HLA–B27' but that's not definitive because you can have HLA–B27 and SpA, or HLA–B27 and not Spa, or not HLA–B27 but with SpA.

In SpA, some MD researchers are looking into a link between SpA and a starch-loving gut bacteria called Klebsiella that can produce lots of inflammatory effects. In your case, it might also make your MCs overly reactive. Like a rising tide.

You can try keeping a food log. Probably  you already have.

[Ken_PA]

"heat"
I wouldn't try to tough through it anymore, you most likely can't get used to it that way but might make it worse (by upregulating heat receptors on MCs).
Core temperature can get surprisingly very high in exercise, say over 107F as a guess. The intestines have 'heat shock proteins' that can break down and that can lead to leaky gut which leads to generalized inflammation - which can make MCs even more likely to get set off.

[Ken_PA]

"Heat and aspirin/ibuprofen seem to be my most severe triggers."
Salicylates are in some foods (aspirin is acetylsalicylic acid). Did any doc tell you that?

Also histamine in foods is a problem for some. There was e.g. the "Low Histamine Chef".

[Ken_PA]

"I just have some anxiety that within a year or two I might find out, for example, that I had some kind of cancer that might have been treatment responsive if caught earlier but now it's too late."

I don't see that being involved here at all.

And btw, it was perfectly fine for you to post your case on this forum :) Feel free with any questions whatsoever.

[Ken_PA]

"but this left-side situation just tends to freak me out, mainly because of the swelling"
Yes, there is something different in the tissue on that side. Something odd.

Now consider this: there is no direct communication between the arm and the ear on that side. Why does the inner ear swell the same way the arm does? Why not both ears? Anything odd in your history? Any infection or toxins or impact trauma?

(Lymph fluid flows up the arm, over into a major vein then into the heart.)

[ArtistLike]

My cardiologist felt strongly that the pain on my left side, but not the swelling, is nerve related. I have cervical spondylosis (arthritis in my neck), diagnosed when I was 33. I am 42 now. I understand that the pain and other nerve problems likely are caused or exacerbated by that. What throws me and concerns me is the swelling in the same areas. It seems like a really odd coincidence.

[Ken_PA]

Are you certain that the "gyno" is really hormone mediated fat deposition, and not just water/edema? Or maybe there is a base of fat and then also edema occurs during episodes?

I don't know if a mammogram can distinguish between water and fat there, but an ultrasound likely could. We know that fat could not suddenly increase then suddenly go away.

[ArtistLike]

I had a mammogram of both breasts and an ultrasound of the left breast performed by a breast cancer specialist at a radiology center. She told me I have gynecomastia in both breasts, much more pronounced in the left breast. She said gynecomastia is not fatty tissue; it is abnormal growth of denser breast tissue. She said almost the entire rest of both breasts is fatty tissue. She said that is all good news from a health perspective given that she sees no tumors, cysts, fibrous tissue, etc.

I feel like my entire body experiences edema, swelling to greater and lesser extents at different times. I don't know if it is related to diet or what.

[Ken_PA]

' If it's "only" that, then I certainly can keep living with it."
Well, no. You should be carrying an Epi-pen or similar. You don't know how much worse it might suddenly get.

The severe swelling might damage blood vessels or other tissue.

You also are experiencing repeated bouts of severe inflammation and possibly chronic low level inflammation that can bring long term problems, such as increased risk for heart and cancer. What are your CRP, hs-CRP, and ESR blood tests?

You should absolutely want to figure this out and counter it as much as you can, if possible. Absolutely.

I'd just find one or two of the Afrin talks on youtube, no reason to read the book.

What if you apply heat on the arm? MCs do have heat and cold receptors, of course. Over one hundred receptor types known so far and two hundred mediators that get released.

[ArtistLike]

I don't know those blood test results. I will consult with my doctor in a couple of weeks and will ask about those values. My tryptase count is reliably high, around 17, I think. My c4a is high on and off, always with a normal c3a. (My doctor began testing this in 2015 when I was treated for Lyme disease and Bartonella infections, which seem to have been treated successfully based on permanent resolution of a lot of symptoms, but MCAS symptoms have persisted.)

Heat applied locally to my skin has the same effect as scratching it: I break out in hives locally, often but not always then spreading and becoming bodywide flushing, itching and sometimes hives.

I am effectively allergic to heat, both environmental and exercise induced. The effect of extended heating up is usually the same: I itch, then I flush, then my nose runs, I get light headed:dizzy, I get hives, my vision blurs and I begin to gasp for air. I cough when drinking water at this point, but drinking cold water helps to cool me dowj and end the reaction. A few times, I have gotten Parkinson's-like tremors--visible and uncontrollable ones--when I am overheated. Heat and aspirin/ibuprofen seem to be my most severe triggers.

[Ken_PA]

One thing I'd wonder is if there is one-sided lymphadema that is causing the swelling because of something like closed valves, or if instead it is just the more usual swelling based on inflammatory mediators like histamine.

[ArtistLike]

Thank you. I appreciate your thoughtful response. I do need to read Dr. Afrin's book. I'm used to having a lot of strange symptoms that range from annoying to painful to limiting, but this left-side situation just tends to freak me out, mainly because of the swelling. The breast is very significantly swollen and the arm less so, but it swells enormously when I heat up. It's so alien.  It has swollen so much twice while I was exercising on an elliptical machine that I could only slightly bend it at the elbow--it was just puffed up like a balloon . The swelling went down when I cooled down. That was my first notion of lymph involvement, but just as you said, my doctor said it sounded like a serious histamine response. If it's "only" that, then I certainly can keep living with it. I just have some anxiety that within a year or two I might find out, for example, that I had some kind of cancer that might have been treatment responsive if caught earlier but now it's too late. It's just worry, I guess. Thank you again. I really appreciate your responses.

[Ken_PA]

"I'm just seeking some sort of resolution and appreciate any insights anyone can offer."

Hi, for starters I'd point out that noted MCAS doc Afrin uses the principle of Occam's Razor in the title of his book. So that supports the idea that it's wise to assume at first that the MCAS is related to everything, unless there's compelling reason to figure otherwise. You can, e.g., even find patients with only tinnitis who are online saying that their own tinnitis is inflammatory.

I don't think you should look for a particular specialty, but rather nope to get the right individual doctor. But finding a Diagnostician might be a good direction to go. Or an Internist who bills themselves as "Functional Medicine". But then again it's also possible that by chance an ER nurse might know something very valuable to your case.

I'd try mast cell stabilizers to see if there's any benefit. The granddaddy of MCAD, Dr. Theoharides, focused on using luteolin. There's also quercetin. They are OTC.

"...severe pain in my left arm, shoulder, neck, jaw and chest, my doctor also referred me to a cardiovascular specialist." Right, because it's prudent to rule out something very dangerous, even though that was not ever the most likely cause. Inflammatory substances like bradykinin and Substance P caused your pain, most likely.

There is a lot of overlap between MCAS and some cases of Chronic Fatigue Syndrome and/or Fibromyalgia. You might find it interesting that CFS was almost renamed to Systemic Exertion Intolerance Disease. That points to a biochemical trigger, rather than a mechanical trigger - but you can e.g. try a single set of medium weight bicep curls to see if that causes eventual severe pain. That's different than exercise metabolites from endurance training. Those sort of self-experiments can provide useful clues.


"just in case specialists..."
Nope, no doctors are here.