Quite a few interesting studies in the April 1 issue of “Blood.” One of them (see abstract: http://tinyurl.com/2sshyj) examines the risk that white and black male U.S. vets with prior autoimmune, infectious, inflammatory and allergic disorders have of developing multiple myeloma or MGUS. The researchers looked at the computerized discharge records of more than four and a half MILLION vets (between 1969 and 1996). They found 4641 patients who were discharged with a diagnosis of myeloma, and 2046 with MGUS. They looked only at the above-mentioned type of patient (some patients, such as women, were excluded due to small percentages; furthermore, those who had cancer at admission or developed cancer or died within the fist year were not included). You can read some of the results in the abstract, so let me have a look at the full study, for which I am indebted as usual to Sherlock.
Benign, asymptomatic MGUS is thought to be the first pathogenetic step in the development of most, if not all MM; however, the specific trigger that initiates the progression from MGUS to MM is unknown.
Skipping the usual dire statistics, let’s go to a more interesting part: Several studies have investigated the hypothesis that repeated or chronic stimulation of the immune system may lead to MM. Some studies have observed elevated risks for categories of immune-stimulating medical conditions (eg, autoimmune conditions, infections, and allergies) or for specific immune-stimulating medical conditions (eg, rheumatoid arthritis and eczema); however, results have generally been inconsistent. This has been a recurrent topic on the myeloma patient lists: is it a good thing to take immune system stimulators (medicinal mushrooms, e.g.) when our immune systems are already over-stimulated? I confess I haven’t come up with a satisfactory answer yet (although I have a gut feeling about it 
), and would be glad to read any and all opinions.
), and would be glad to read any and all opinions.Study results: patients with previous autoimmune diseases had an elevated risk of developing myeloma. Statistically elevated risks were also observed for the following specific autoimmune diseases: polymyositis/dermatomyositis, systemicsclerosis, autoimmune hemolytic anemia, pernicious anemia, and ankylosing spondylitis. Where numbers allowed comparison, risks were generally similar for white and black men.
And read this: Risks were also significantly elevated for both races combined for prior infectious disorders, specifically pneumonia, hepatitis, meningitis, septicemia, herpes zoster, and poliomyelitis Risk of influenza was significantly elevated for white men, but not for both races combined. The flu, a possible trigger? Yep, the relative risk is 1.18.
As for inflammatory ailments and allergies, There was a statistically increased risk of 18% associated with inflammatory disorders, largely due to significantly elevated risks for osteoarthritis (the most commonly reported disorder in our dataset) glomerulonephritis, and nephrotic syndrome. There were no significant elevations in risk for allergies overall or for any specific allergies for both races combined. For the five patients with celiac disease, the relative risk was 2.07. That’s quite high, actually. Compare that to the 34 patients with psoriasis, whose relative risk was 0.86. Ailments of the respiratory system were also considered, from sinusitis (RR: 1.17) to pneumonia (RR: 1.54).
Asthma, which I have (guess what? I’m allergic to CATS, no kidding! In order have cats in my life, I must use a cortisone inhaler once a day and Ventolin whenever necessary, although matters have vastly improved since I began taking curcumin), is also mentioned (RR: 0.98). Heck, even having urticaria puts you somewhat at risk!
Interesting titbit in the Discussion part: There is also the possibility that treatment for certain conditions rather than the condition itself may increase susceptibility to MM. For example, we previously reported an increased risk of MM among Connecticut women following use of steroids. Hmmm, so the risk of developing myeloma is due in some cases more to the treatment (prednisone, as the study suggests) than the disease itself. How about that?
Another good one: Our observation of an association between MM/MGUS and specific prior bacterial or viral infections suggest that these infectious conditions may be a potential trigger for MM/MGUS development or a manifestation of underlying immune disturbances due to undetected MM or late-stage MGUS. Recurrent infections largely of bacterial origin (septicemia, meningitis, and pneumonia) are often part of the natural history of MM. This study and a previous Danish one found that patients with a history of pneumonia had a more elevated risk of developing MGUS, which suggests that pneumonia could be a precipitating event for the development of MGUS.
The biggest drawback of this study, apart from the focus on a certain population (don’t you just love this sentence: The exclusion of women might limit the generalizability of our results. Just “might,” huh? 
), was the fact that the researchers didn’t have access to any medical records. Theirs was a computerized study, period. But I found it interesting, and besides, it gave me a break from another study that is driving me up the wall (I am spending heaps of time looking up the meaning of about a zillion acronyms and medical terms that I do not recognize; sigh, why can’t studies be written in plain English…or Italian?).
), was the fact that the researchers didn’t have access to any medical records. Theirs was a computerized study, period. But I found it interesting, and besides, it gave me a break from another study that is driving me up the wall (I am spending heaps of time looking up the meaning of about a zillion acronyms and medical terms that I do not recognize; sigh, why can’t studies be written in plain English…or Italian?).I would like to add that I am only moderately curious as to how I developed cancer. I have it, I am trying to DO something about it, and life goes on. Only time will tell if what I am doing will keep me stable. But sometimes I wonder: if I could figure out what triggered it…well, could that possibly help me fight the cancer now? (I have excluded a few possible triggers already, such as H. pylori.) Was it triggered by a general weakening of my immune system caused by allergies or by the case of Epstein Barr I had in grad school? Or were these “underlying causes” (see below)? I suppose one could really go berserk thinking about possible triggers blablabla. Therefore, I am just going to forget about the issue. I have better things to do.
Study conclusion (RA is rheumatoid arthritis, by the way): In summary, we found significantly elevated risks of MM/MGUS associated with broad categories of autoimmune, infectious, and inflammatory disorders, but not with allergic conditions or RA. We also observed significantly elevated risks for a number of specific autoimmune disorders. Some of these disorders may be a potential trigger for MM/MGUS development, while others may represent underlying conditions due to undetected MM or late-stage MGUS. These results highlight the need to explore the pathologic mechanisms underlying the association of these diseases with MM/MGUS and to consider the diagnosis of MM/MGUS in patients presenting with these conditions.
I know what you mean about having to look stuff up all the time. My friends are amazed by what I now know about my type of cancer. I spend so much time just looking up the meaning, and then about 10 times reading the abstract to make sure I am getting it right, plain english would be so nice to have.
J Bioenerg Biomembr. 2007 Jun;39(3):211-22.
Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers’ most common phenotypes, the “Warburg Effect”, i.e., elevated glycolysis in the presence of oxygen.
Very interesting article. See what you think.
Be well
Hey!
Yes, as I already told you Margaret, I (and also 3 different doctors from different areas I visited) suspect EBV to be the trigger of my MGUS. I got mono in 1993 and I’m not being well ever since, not all the time of course, but in some intervals, without a pattern.
There’s also an old CMV (cytomegalo-virus) infection present in my blood results.
And I also had a meningitis while doing a military service back in 1988.
Doctors say that EBV is capable of changing a human DNA… Well, who knows.
So I kissed the girl once upon a time and it was “a kiss of death”…
Have a nice spring, ciao!
Robert
I think the trigger is very important Margaret. If you recall from the recent email I sent you, monoclonal paraproteins can be specific to an antigen just like normal antibodies. Has anyone had their paraprotein tested for antigen type by the way? (I have a call in to my hematologist at the moment). If we could find out what the antigen was it might be a focus for prevention or cure. For example, if the antigen was a celiac protein, it would be worth trying a gluten free diet. If it’s a virus like EBV it might be a problem, because that can stay with you for life, but there must be ways to keep it quiet.
Hi Paul!
Yes, I think you’re absolutely right. About the EBV and relative viruses: my experience with doctors from different fields is that they have very different points of view and also approach to the matter. In past years I was sent from hematologist to infectologist and internist and back and forward. Many of them tested me for so called “titres” for EBV, CMV, hepatitis virus etc. Results varied, but the interpretation was so different! If the hematologist claimed I was having some kind of a chronic mononucleosis – each time my immune system is “down”, the EBV is reactivated and the illness is back- the infectologist (or whatever is called in English) completely disproved this statement saying that is not possible and that titres are always active and they go up and down normally.
And there I was in the middle of professional arguing with no firm diagnosis and still feeling very bad from time to time.
Right now I’m undergoing an immunological therapy aiming also the CMV and the titres have gone significantly up, actually they’ve doubled. So there MUST be some reason other than just “normal varying” I think. The doctor is satisfied, but I’m not as much for I feel flu-like all the time. 🙁
Don’t know for how long more, but I hope not too long.
Stay well everyone and enjoy the spring!
Robert
I guess it was a foregone conclusion that I would end up with MGUS. I have the following autoimmune conditions: lupus, CREST syndrome (which is a mild form of systemic slerosis), Hashimoto’s thyroiditis, and now probable Sjogren’s syndrome with tear volume 1/3 of the normal minimum). And I seem to recall someone else earlier on this blog commenting about his dry, sticky eyes! Was that Paul?
There is a good explanation of “relative risk” at http://www.proteinpower.com/drmike/uncategorized/relative-risk/
That article explains that when there is no increase or decrease in risk over what would be present in the population overall, R = 1. An R greater than 1 would signify increased risk and an R less than one would actually signify a reduced risk in comparison with the general population.
Margaret, your use of the cortisone inhaler (a steroid) definitely placed you at greater risk for developing MM according to what I have read also. Probably steroids dampen the ability to mount a successful immune response to SOX-2 on the aberrant stem cells (see Dr. Dhodapkar’s findings). Isn’t it interesting then that steroids are used in chemotherapy approaches toward MM?! Apparently they only become of advantage when the aberrant immune cells have gotten the upper hand!
I still have MGUS and not myeloma, but the specialist I see for monitoring the MGUS keeps telling me that I should let my rheumatologist use immunosuppression for my autoimmune disease. And I said, “No way Jose! I want to retain my immune response against SOX-2!” I couldn’t believe his reply. He said, “But if even if you do progress to MM, you’ll still have about 8 years with current therapy.”
“Not acceptable!!!” I cried. I am only 59, and all my ancestors have lived well into their 80’s and 90’s. I’d be horribly cheated!” So far my rheumatologist seems to understand my point of view on this and is content to monitor my liver and kidneys which are still only very slightly affected by the autoimmune problems. Furthermore, how do we know that the increased risk for people with autoimmune problems isn’t due MOSTLY to the steroids generally used on them?! Has anyone ever done a study that shows the relative risk for developing MM in autoimmune disease treated with immunosuppressives vs. autoimmune disease left untreated and only monitored?!
The part about flu is very interesting also. My autoimmune symptoms really got going 14 days after a flu shot – just exactly the amount of time it takes for the immune response to kick in. I developed rotator cuff inflammation that lasted for months. Finally I went for the first time to a rheumatologist, who put a steroid shot into my shoulder, and whose blood testing showed that my ANA (antinuclear antibodies) had shot up to 2560 (over 30 is abnormal) making me a lupus suspect. My internist, though, would not believe me, and insisted on giving me a flu shot again the next year. And again, exactly 14 days later I had the rotator cuff problem recur. And another steroid shot. The MGUS was discovered just a couple years later when my autoimmune symptoms suddenly intensified.
As for celiac disease, I don’t have that, but interestingly I do have one of the two genes most notorious for causing it. So I’ve gone gluten free, hoping to mitigate my other autoimmune diseases which are also associated with this particular gene.
Paul, if you can ever find a doctor who can determine antigen type from my paraprotein, please let me know via Margaret! I would love to know what, if not gluten, is causing my autoimmune disease, for so far, eliminating gluten hasn’t changed things much. Perhaps it’s too early to tell, though. It would be nice to be able to eliminate something from my diet, and have all this simply go away.
Sorry to go on so long, but this article was thought provoking in many ways.