Respiratory Tract Infections And Shingles Linked To An Increased Risk Of Developing Multiple Myeloma
Findings from a recent study indicate that a history of certain infections is associated with an increased risk of a person eventually developing multiple myeloma.
The study is based on data for more than 15,000 U.S. myeloma patients and 200,000 people from the general U.S. population. It did not include in its analysis infections that myeloma patients had less than a year prior to their diagnosis.
The investigators found that people in the study who were eventually diagnosed with multiple myeloma were more likely to have had respiratory tract infections or shingles one year or more prior to their diagnosis than individuals of a similar age and gender from the general population.
In addition, a history of infections was associated with a higher risk of being diagnosed with myeloma even when the researchers looked only at infections that occurred several years prior to a patient being diagnosed with myeloma.
These findings – particularly the significance of infections several years prior to a myeloma diagnosis – suggest that infection may play a role in the development multiple myeloma, the investigators explain. Bacteria or viruses that cause infections may play a direct role in bringing about the onset of myeloma, or their impact may be indirect, perhaps through the inflammations they cause.
The authors also note, however, that their findings may also be a reflection of myeloma, even in its earliest stages, compromising a patient's immune system, making the patient more likely to develop infections. The infections "may instead be a manifestation of an underlying immune disturbance present several years before multiple myeloma diagnosis and thereby part of the natural history of disease progression."
Background
It is well known that patients with multiple myeloma are more susceptible to infections due to their weakened immune systems. Cancerous myeloma cells accumulate in a patient's bone marrow, where they limit production of healthy red and white blood cells. Since white blood cells are responsible for the production of antibodies, the body’s ability to fight pathogens is limited.
It is less clear whether a long-term history of certain infections is associated with a person having an increased risk of developing multiple myeloma.
On the one hand, there have been a number of studies that show that a history of pneumonia is associated with a higher risk of developing both multiple myeloma and its precursor disease monoclonal gammopathy of undetermined significance (MGUS).
On the other hand, results for a number of other types of infections, and their potential association with developing myeloma, are less consistent -- in part because previous studies have been limited by small sample sizes.
Thus, the authors of the current study decided to analyze records for very large samples of multiple myeloma patients and healthy individuals to determine if there was an association between a history of infections and the development of multiple myeloma.
Study Design
For their study, the investigators from Queens University in Belfast, Northern Ireland and the U.S. National Cancer Institute (NCI) drew on data from two different sources.
The first was the NCI's SEER-Medicare database. The NCI created the SEER-Medicare dataset by linking patient records from the Surveillance, Epidemiology, and End Results (SEER) database, which is a key source of U.S. cancer statistics, with beneficiary claims records from the U.S. Medicare program -- the federally funded health insurance system for U.S. citizens 65 years of age and older.
The SEER-Medicare database provided information on 15,318 multiple myeloma patients who were diagnosed between 1992 and 2005, and who were 66 years of age or older at the time of their diagnosis. Approximately two-thirds of the myeloma patients (64 percent) were diagnosed between 1999 and 2005.
The Medicare data in the SEER-Medicare database enabled the researchers to determine how often each patient in the database visited a hospital or physician's office due to an infection in the years prior to the patient being diagnosed with myeloma.
The second source of data the researchers drew upon was a companion database of Medicare beneficiary claims that the NCI developed specifically to enable comparisons with the SEER-Medicare database. This companion Medicare database includes records for a randomly selected sample of 5 percent of all Medicare beneficiaries over the relevant period.
From the comparison Medicare database, the researchers selected claims for 200,000 people matched to the myeloma patients in the SEER-Medicare database based on age and gender.
The median ages of the patients in the SEER-Medicare dataset and the matched Medicare dataset were both between 75 to 79 years old. The investigators recognize in their article that the older age of the patients in their study may limit the degree to which their results can be generalized to all myeloma patients. In the U.S., the median age of a myeloma patient at diagnosis is 69.
The study's analysis was restricted to infections that occurred more than 13 months before a myeloma patient's diagnosis. The researchers looked at both the entire available history of a patient's infections 13 or more months prior to diagnosis, as well as infections recorded during four defined periods of time prior to diagnosis: 13 to 30 months, 31 to 48 months, 49 to 72 months, and more than 72 months (six years).
The infections analyzed by the researchers included respiratory tract infections, gastrointestinal infections, urinary tract infections, and skin infections.
Results
Overall, myeloma patients were more likely than the general population to have a history of respiratory tract infections (such as bronchitis, influenza, pneumonia, and sinus infections), shingles (herpes zoster infection), and cystitis (lower urinary tract infection).
The researchers observed the strongest association between a history of shingles and the development of multiple myeloma. People diagnosed with myeloma were 39 percent more likely to have a history of shingles than age- and gender-matched members of the general population.
Likewise, a history of pneumonia was 27 percent more likely among myeloma patients compared to the general population, and cases of the flu (influenza) were 18 percent more likely among myeloma patients.
On the other hand, a history of the common cold, kidney infections, or gastrointestinal infections was not significantly more likely in myeloma patients compared to the general population.
The researchers also found that a history of shingles, pneumonia, bronchitis, and sinus infections was consistently more likely among myeloma patients, compared to the general population, across all the specific time periods prior to diagnosis that they analyzed -- even six years and longer before diagnosis.
Indeed, the researchers found that myeloma patients were particularly more likely than the general population to have shingles (a 48 percent greater likelihood), pneumonia (41 percent), bronchitis (29 percent), and sinus infections (28 percent) in the period 31 to 48 months prior to diagnosis.
The authors note that the latter findings may indicate that a myeloma patient's immune system is weakest during the 31 to 48-month period prior to diagnosis.
Or it may indicate that certain infections during this period are particularly likely to initiate processes that eventually lead to the development of multiple myeloma.
Infections As A Risk Factor For Myeloma?
The study authors are clear in their article that their findings do not prove that infections lead to a greater risk of myeloma. It is possible, they admit, that causality may run in the other direction -- that is, that undiagnosed, still-developing multiple myeloma may increase a person's risk of infections prior to a myeloma diagnosis.
Nevertheless, the investigators lean toward interpreting their results as indicating that infection may, in fact, increase the risk of multiple myeloma.
One key finding of their study in favor of this view, they argue, is the fact that myeloma patients are more likely to have a history of infections far in advance of their eventual diagnosis. It seems "unlikely," the researchers argue, that undiagnosed myeloma could lead to a higher risk of infections so long before the disease becomes symptomatic.
In addition, the investigators note that shingles -- which in their study was found to be particularly associated with the later development of myeloma -- also has been linked to other blood cancers, including certain forms of lymphoma and leukemia.
Likewise, inflammation, which is one of the body's reactions to infection, is well-established as a promoter of several types of cancer, the authors note. In this regard, the researchers point to their finding that a number of different infections are associated with an increased risk of myeloma, and most of those infections are not due to a single virus or bacteria.
This, the investigators write, suggests "that inflammation rather than exposure to a particular antigen may be associated with the malignant transformation to multiple myeloma."
For more information, please refer to the study in the International Journal of Cancer (abstract).
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My son who is 39 has had the shingles 4 times. He is not the one with multiple myeloma. His sister who was diagnosed at 32 has myeloma. She has never had shingles or respiratory infections. Now I am nervous for my son although this article sounds a little bit like which came first - myeloma or the shingles.
This is kinda interesting to me. I am 54 years old and was diagnosed in March 2012, although I know I had it as early as Christmas 2010. Now this is no joke. I have had a fever, cold ... anything ONE time from age 17 - 52. In 1986 I had strep and that is it. I have NEVER missed a day of work sick in my life. Even currently, after SCT, chemo, radiation, I still have not had a fever or cold. NOTHING. I went back to work 30 days after transplant, did not get sick from chemo. All I can say is this is a strange disease, I feel better today then when I was 25 and I find myself sitting and waiting for the ax to fall. When will I feel bad, when will I get sick, neuropathy, tired (I did get a little tired during transplant). Besides my bad back ... that will never be right again ... I would love to feel the way I do right now forever. But I know the stuff will hit the fan eventually and I hate the thought!
My husband was diagnosed in Sep 2012. He is 50 never been sick no colds or fevers I reed many testimonials of MM patients and they were healthy before they were diagnosed. I wonder: How accurate is this study?
Hi Terri, Hugh, and Mary Ann. Thanks for your comments.
Terri - You are correct that the study does not draw a definite conclusion as to whether myeloma is (in part) caused by infections, or whether infections happen more often because someone already has the early, undetected, stages of myeloma. This is question that will need to be answered by future research.
There is no reason to be unduly concerned about your son's health based on the results of this study. Your son should probably discuss with his doctor the fact that he's had shingles so often, and he may want to mention that his sister has myeloma. The doctor will know what's best to do given that information.
Hugh - Congratulations on doing so well despite your myeloma diagnosis and the treatments you've had. We hope you continue to stay healthy and strong for a very, very long time!
Mary Ann - The study discussed in the Beacon's article uses data for a very large number of myeloma patients and for a very large number of people from the general population. The study also was carried out by very reputable researchers. So it's fair to assume it's accurate.
That said, the study doesn't say that everyone who has myeloma had infections prior to their diagnosis, nor does it say that everyone who has infections will eventually develop myeloma.
All it says is that people with a history of certain infections seem to be more likely to develop myeloma.
You can think of it this way. For everyone, whether or not myeloma occurs is like a flip of a coin. The chance that the coin comes up "myeloma" is very low for everyone. But, for people with a history of certain infections, the chance that it comes up "myeloma" seems to be higher.
This also means, by the way, that many people who have been perfectly healthy, with no infections, will still have their coin flip come up "myeloma" (unfortunately).
The real beginning for me I believe was when I developed a disseminated HSV 1 infection after someone drank out of my water bottle at a dance club (2002)
Then I had shingles in 2004.
After having shingles I started getting all these "weird" infections. I was supposed to be young and healthy (late 20's) but I was constantly going to the dr. I was told once my white count was low, but not that low.
In winter 2007 I had a chronic ear infection that led to frequent sinus infectios, popped ear drum and horrible vertigo attacks. MRI showed a mastoid infection (chronic ear infection in the bone)
I was finally diagnosed with stage II Multiple Myeloma in January 2010. I've continued to develop infections during the course of my disease, though I am in Remission now for a few years. I see an infectious disease transplant dr. who monitors me along with my Oncologist.
This article really grabbed my attention. I developed shingles around my 40th birthday about 4 years before I developed multiple myeloma. In the year before my multiple myeloma diagnosis I had chronic sinusitis for over a year and had been getting sick far more often that I normally do. It was the results of the CBC test done for my sinus surgery to help resolve the sinusitis that lead to me being diagnosed with stage thee myeloma the following month. My case seems to be exactly what this article is talking about.
lsys2012,
Reading you case reminded my of something I had forgot. I also had a really bad case of some kind of oral herpies virus I beleive about a year before I had shingles. They has prescribed Acyclovir to treat it and that was the first time I had heard of that medication. So to review we both:
Had a HSV1 infection
Followed by a Shingles infection
Followed by frequent chronic sinus infections
Followed by Multiple myeloma
What are the odds of that being just a coincidence?
The point of this study for me is to remind clinicians (and patients) that the differential diagnosis of new, unexplained infections (bacterial or viral) should include hematologic diseases, including multiple myeloma. Most MM patients will not present this way, however. And there are of course many other causes, including AIDS, to consider.
More common is the classical CRAB symptom presentation: elevated calcium and renal tests, anemia, and bone pain. As many of us know, delayed diagnosis of MM is still frequent. Persistent rib or musculoskeletal pain not responsive to manipulative therapies should raise red flags. Experienced physicians are more likely to recognize subtle presentations of this and other diseases.
Thanks, everyone, for sharing more about your own personal experiences and insights related to the study. The additional perspective provided by your comments is very helpful.
All of this is thought provoking. I presented because I fractured a bone in my neck and they found a tumor at the base of my skull- in the bone at age 53 (2011). Very painful. Besides that I had no symptoms, HOWEVER, I was always getting strep throat and other respiratory infections as a kid and adult and find my throat/neck to be my weakest area. After having the stem cell I seem pretty healthy, like Hugh S mentioned, but I wonder if that is attributed to healthier eating, exercise, staying away from unhealthy folks as much as possible, etc?
I can say I considered myself healthy to before I got my diagnosis of Multiple Myeloma. I had recently been discharged from the hospital where I was admitted for pneumonia in 2009. Because of my blood work continued to be abnormal I was referred to a hematologist in 2010. He did a bone marrow biopsy and told me I had multiple myeloma.
In March of 2006, three years before my diagnosis, I had a respiratory infection followed by rib pain. The physician I saw took an xray and said it was pleurisy. The rib pain never went away. The following Christmas I was diagnosed with arthritis but that may have been a misdiagnosis because in March 2009 I was diagnosed with non-secretory multiple myeloma.
"Cancer", I believe, is at its root a disease of the immune system. Something goes awry and a person's immune system no longer recognizes cancer cells as something that needs to be responded to. So, it makes sense that certain infections can cause changes in a person's immune system.
I had a terrible case of shingles almost exactly one-year to being diagnosed with multiple myeloma. Prior to the shingles, I was an active 70 year old playing tennis four times a week, working out three times a week, bowling, etc. After the shingles, my health significantly deteriorated and I can no longer play tennis. My weight is down 35 pounds and I am now anemic which can in part be attributed to the chemo treatment. This article was an eye-opener for me.
My diagnosis, in a word, has baffled my doctors. They tell me regularly that my symptoms or presentation are not normal for MM. But after reading this article, a lot of it rings true for me. Sinusitis, pneumonia, shingles -- I had them all before being diagnosed. Fortunately, I have not had organ or bone trouble to date. So thanks for the clarity. Maybe I should forward this article to my doctors. Lol
Glad the article was of some help, Vicki. Best of luck to you!