What Causes Rheumatoid Arthritis to Trigger?
What causes Rheumatoid Arthritis? (UPDATED)
I never asked “why me?” when diagnosed with RA because it’s not my way of thinking. Yet people do ask me “HOW did this happen?” or “What triggers RA?” What causes rheumatoid arthritis – that’s the multi-billion dollar question! Here’s a summary of what is known at this point. There are a lot of studies quoted here, so you may want to bookmark this page for future reference.
1. WHAT happens when Rheumatoid Arthritis begins?
Researchers have been puzzled for years about what causes Rheumatoid Arthritis (RA). They’ve found certain areas in genes that seem to be connected with RA.
Regions in the genome have been identified which frequently are associated with RA. However, environmental triggers are still considered the necessary missing link. What triggers Rheumatoid Arthritis onset in some? What determines the disease course? This is important in the search for ways the process of RA can be derailed.
Some researchers speculate that a type of switch might “turn on” the process of inflammation through citrullination. However, one problem with identifying what triggers this process is that auto-antibodies such as Rheumatoid factor and anti-CCP (ACPA) can appear more than a decade before the arthritis symptoms of RA become obvious. So people may experience the disease before the blood tests can detect it. “A pattern of systemic inflammation is also apparent in pre-RA patients as determined by the multiplex analysis of cytokines in the serum.” They call it “pre-RA” because people are not diagnosed yet, but the RA is already there.
A 2005 study in the British Society for Immunology examined Early environmental factors and rheumatoid arthritis: “Estimates suggest that the risk of developing RA is at most 50% determined by genes. “There has been limited success defining the environmental factors important in developing RA. We hypothesize that this lack of success may be due to a concentration on the time around disease onset. There is evidence of production of the autoantibodies rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP) and increased levels of C-reactive protein (CRP) years before RA becomes clinically apparent.”
Gene changes and the development of autoimmune rheumatic diseases
Could our DNA be changed by our environment? Could that affect whether we develop RA?
The “switch” may be an epigenetic mechanism. That’s a change in gene expression caused by a mechanism other than an underlying DNA sequence. The very basic idea is that something in the environment might turn a gene on or off. “The potential roles of epigenetic alterations in the pathogenesis of autoimmune rheumatic diseases are raising great expectations among clinicians and researchers. Epigenetic mechanisms regulate gene expression and are sensitive to external stimuli, bridging the gap between environmental and genetic factors. Considerable evidence of epigenetic changes, particularly altered patterns of DNA methylation, exists in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis,” Nat. Rev. Rheum.
2. WHERE does the Rheumatoid disease process begin? Connections are seen with…
What causes Rheumatoid Arthritis to spread through the body? Could it begin in another part of the body and then spread to the joints? Here are 3 areas that have been studied.
- RA and periodontal disease.
- RA and inflammation in the lungs.
- RA and the digestive tract: “New insights from DNA sequence-based analyses of gut microbial communities and a renewed interest in mucosal immunology suggest that the microbiome represents an important environmental factor that can influence autoimmune disease manifestation,” Nature Reviews Rheumatology.
3. WHAT causes RA to begin?
It’s possible that exposures to different substances over years work together to trigger RA in some people.
As shown in the screen shot here, Rheumatoid Arthritis disease activity precedes diagnosis by years, so earlier events must be examined as RA triggers. A Swedish study highlights the need to study the interaction between genes associated with RA and environmental triggers: “The data… highlight the need to study putative environmental stimuli that may act over many years, as well as the genetic contexts that may permit these agents to exert proarthritogenic effects.”
In a new study published at ACR 2011, Swedish and American researchers reported they “found no evidence of an increased risk of RA related to particulate air pollution.” However, modest increases in RA risk were found with higher exposure to sulfur dioxide when considering several years prior to “onset.”
SUMMARY: What Causes Rheumatoid Arthritis? Possible RA triggers
So what causes Rheumatoid Arthritis may not be the same in each person. A combination of factors may be to blame, but here are some triggers that have been investigated.
- Smoking is specifically linked to RA and citrullination: “This study provides evidence that smoking enhances PAD2 expression in the bronchial mucosal and alveolar compartment, with consequent generation of citrullinated proteins in the latter. Smoking is an environmental factor that may lead to citrulline autoimmunity in genetically susceptible subjects,” NIH.
- Insecticides are associated with increased risk of Lupus and RA.
- “Personal insecticide use correlates with increased risk of autoimmune rheumatic disease with stronger associations among those with a greater frequency” of use, as reported at the 2009 ACR meeting.
- Exposure to traffic pollution brings an increased risk of Rheumatoid Arthritis, even in non-smoking women who are Rheumatoid factor negative. Women in this study lived within 50 meters of a road.
- Living near an airport is widely reported as associating with RA incidence.
- Not only does smoking increase risk of RA, more smoking associates with more unrelenting, severe RA, Rheumatoid factor, and higher anti-CCP.
- Chemicals such as those in hairspray and lipstick are associated.
- Hair coloring: “Hair dye linked to rheumatoid arthritis,” New Scientist.
- Men who work with asbestos and mineral dust had a higher hazard risk for RA, as did women in printmaking.
- As I update this list in 2016, a recent study found textile dust linked to a higher incidence of RA.
Strongly recommended:
- Digging in to the 2011 American College of Rheumatology Scientific Meeting
- Guest genetics series: An Introduction to the Genetics of Rheumatoid Arthritis (RA)
- Causes of Rheumatoid Arthritis: Are There New Clues?
- ACR REF Rheum Research & Courage That Won’t Back Down
My doctors thought I had lung cancer because of lung nodules but they were actually RA nodules – does anyone know of the incidents of this happening?
Pegylated Interferon 2A (Pegasys) triggered my RA.
I believe there are more environmental factors than these that trigger RA. I grew up in a town that has higher than normal radiation levels and I grew up in a very abusive home. Stress from child abuse never really leaves a person and I think it can turn a body on itself. I have not proof of this though. Also, studies done on higher than normal radiation exposure is causing a higher incidence of thyroid diseases, cancer and autoimmune diseases.
I have severe RA and smoked for 22 yrs (stopped 10 months ago), as a child played within 100 yards of a corp dusters taking off and landing spot, insecticide storage, and next to fields when as they were sprayed. Interesting facts!
Hi Kelly
You’ve provided some interesting data and links.
I’ve had severe, non-remitting RA for 20 years now. Certainly there is a genetic component (my sister has RA as well, and 3 more siblings have different auto-immune diseases. Environment while we were growing up was highly suspect as we grew up nearby to a major chemical refinery and my mother was also a chain smoker, so air quality was non-existent.
But I am certain that the trigger to activate the RA was viral exposure. I was healthy and active to the age of 30, when my children and husband contracted chickenpox – and I then developed shingles. Within weeks of the shingles onset, I started having joint pain in my big toes. Four months after that the joint pain was everywhere and profoundly disabling. My RA did not respond to any treatment for the next 8 years until biologics were created, which have helped so much, but unfortunately have not stopped my RA from going extra-articular…now affecting my heart.
Dear Christine, thanks so much for sharing your story. I’m glad you have gotten some benefit from treatments. But yes, we do see that even if joint symptoms seem controlled or remitted, the disease may be progressing silently in other ways. The latest research actually shows the disease does not wait to go extra-articular but actually is systemic and begins outside of the joints. This is one of the several reasons that we must refer to it as Rheumatoid disease instead just of by one of its symptoms, arthritis.
I believe that used engine oil is also a trigger.my onset started after I got a job which included changing car oil,and at the time we didn’t use surgeons gloves .
Great article Kelly. My mom and I were just discussing this the other day. She is sooo determined on finding out where my RA came from. One thing that I have noticed though is that in my teens when I was dx (30 yrs ago) they used my ANA as part of determining factor. You rarely ever hear that discussed anymore. Does everyone that RA have a positive ANA?
nope, many with Rheumatoid have a negative ANA. Mine was positive for years, but that was attributed to thyroid disease. Not sure what was dont 30 years ago, but ANA is not part of diagnosis criteria >> https://www.rawarrior.com/american-college-of-rheumatology-redefines-rheumatoid-arthritis-part-3/
Interesting. My RA was triggered by bronchitis and early pneumonia. Makes you wonder about the lung connection! Hope you’re hanging in there, Kelly!
I definitely got much sicker when I was Bullied out of my 15yr. position at a physicians office. I was one who almost never called in sick(no matter how sick I was with ALL my autoimmune disorders)to having to turn in FMLA paperwork, thinking that would secure my position. At this time she said,”you cost us money”. I only took one day off a week to rest and have more tests done. In between tests I was FIRED… both tests uncovered two more health challenges that are BOTH precancerous in my esophagus. I have since learned a lot about “bullying” and “mobbing”. The practice administrator planed to turn my co-workers against me. She did this(one of the many things she did) by giving them some of the moneys I had earned by a previous 15yr. policy. She told them, not me, so needless to say when I found out I was rather up set and said something, to then, be screamed and yelled at. She had told me one day I looked nice, these were VERY comfortable clothes so I though I would get more. I had them hemmed and also had to get new flats because I could no longer wear my heels. Then she comes up to me and says” your not keeping up with the competition,you need to step it up”. Pointing at my attire… it would have been nice to hear,something like, sorry you can’t wear your heels anymore,that you so dearly love ! She did things like this numerous times and for many more unjust reasons ! I’m sure there are many other people on here who have also been treated in a similar fashion,to all of a sudden, find themselves …Terminated on trumped up charges as an excuse to get rid of chronically ill employees !?! BTW..I’m much better off not working for/with these unscrupulous people and am employed (VERY) part time with very kind caring people !
I believe Rocky Mountain Spotted Fever triggered my RA. Over about a 4 wk period, I had severe inflammation that resulted in the tick fever diagnosis. I was given medicine and completely recovered. I had blood test for RA and was negative. 10 months later the symptoms reappeared,severe inflammation of my hands,stiffness all over, this time the symptoms came full force much faster. I was again blood tested for RA and was negative. My PCP felt I had sero negative RA. I was given meds for tick fever again, but didn’t respond. I waited 5 months to see a rhuematologist. I was given 5 mg of prednosone a day while I waited for the rhuematologist appt. I improved slowly and gained weight (ugh!) The rhuematologist diagnosis was sero-negative RA. He said there was no way to really know if the tick fever had triggered the RA. I feel it did, because my only symptom prior to the tick fever was a frozen shoulder about 10 years prior. I am still on prednisone and now on methotrexate. I am feeling much but certainly battle fatigue. This website has been so helpful in knowing what to expect. Thanks!
Dear Diane, I agree that it’s possible. Any kind of shock to the immune system could possibly be part of a trigger for things to set in motion. I hope the treatment works well for you!
Thanks for a great article and reply posts from so many. I believe my RA was triggered by the overwhelming trauma of being struck by a car while walking in a crosswalk seven months earlier. My life BC (before crash) and before first major RA flare started (February 2012) had always been very active and healthy. I never smoked, was not exposed to pesticides/chemicals, no surgeries or car accidents, and no family history of RA or any other auto-immune related disease. I happened upon two research studies that suggest a strong correlation between incidences of extreme physical trauma preceding RA onset in 20% of patients studied, but am surprised more research is not being done. Any thoughts will be appreciated.
Pingback: Rheumatoid Arthritis and Adverse Childhood Events
I’ve always wondered if there could be a link between the gamma-globulin injection (given to women with negative blood types immediately following the birth of a baby that has a positive blood type) and RA. That was my situation ….. I am 0- and my first born was B+ and I was given the gamma-globulin injection shortly after giving birth, and was diagnosed with RA a few years later while still in my twenties.
I have RA since i was 18mnths old i have suffered a lot through school.i didnt start taking tabs etc till 1980 before i got married
I have taken too many tabs and medication to name i started on gold injections through steriods and now i am on an anti cancer drug which i have every 6 months joint problems still effect my day to day living .hip replacement wrist replacement.im too you for any knee surgery which i want ..my RA specialist is great
I am convinced that my RA was triggered after a bout of diverticulitis. The week of my flareup my hands started to ache and could barely use them. Diagnosed 3 weeks later with RA…..
back in the late 60’s i was dix with itp. my platlete cunt went all the way down to 1100 put on pred but it didn’t help. ended up having a spleenectomy they found 2 spleens and removed both. i had been geeting gangliion cysts in my feet and after one such surgery the dr. decided t do a bipsy. it came back as a-typical fr r a. i was still going to my oconolgist as they thought at first it was not itp but lukemia. i told him the findings of the biopsy and he said i did not have r a. now i know different. i was officially dix’ed with ra lupus and many other a i diseases. it has been a uphill battle for me since, lost vision in both eyes do to retinal vasculitis thank god i have a awesome set of eye docs who are trying to save my eye sight. i have had to open heart surgery to replace my aortic valve caused by both r a a nd lupus. i could go on and on with all the issues i have but nt that it would made any difference in my dix i should have been taken seriously about the cysts. today they know more but not enough.cures need to be found i know it won’t be in my lifetime but am hoping for my son and future grand kids. god help us and bless us all we do need it
Interesting study… I found by accident that my RA symtoms seem to appear with my diet. A few years ago I decided I needed to take off some weight and diet. I was taking methotrexate as most of us do and hated every moment of it (my doctor was wanting me to start injections as well). I chose to follow the Atkins diet as I’d had success in the past. I was eating only meat, green vegetables and nuts at the time. I failed to go to my appointment to refill my meds and have successfully been without for over 2 and a half years. It seems that when I stray away and start adding processed foods into my diet, my flare ups start right back up. Hope this helps someone else. Not once did my doctor ever tell me to try and change my diet…. only try this additional medication.
I will do whatever I can to stay off of the methotrexate… my flare ups remind me to watch what I’m eating and live a healthier lifestyle.
I am 70 years of age now and can tell you for sure it is true that rain or snow- humidity is the worse culprit that one can not do a thing about.
Pingback: #4 What Causes Rheumatoid Arthritis? Do early life events affect risk? - Tumbling the Stone
I guess I am the strange one. No one in my family, maternal nor paternal, has RA as far back as I can research. There was no stress, other than normal young married mom stress, in my life when the RA started, and as for smoking, I’m skeptical about it because smoking has become a “catch-all” for Everything that goes wrong, I just find it hard to believe that smoking causes everything bad, from cancers to early hair graying, to bald tires. (and no, I’m not advocating or taking up for smoking, I’m just saying) And if smoking is such a huge factor, then why don’t all smokers get autoimmune? If the doctors don’t really know, they blame smoking whether its a factor or not. And no, I’m not a smoker, just a very observant reader who had a doctor blame smoking on a condition I had, before he found out I wasn’t a smoker. I’m not saying smoking isn’t bad for you, I just think it gets blamed for things that aren’t related to it. Just saying. Also, my RA doesn’t nor ever has affected my hands, wrists, or fingers. So I’m an odd-ball RA’er. 🙂 And I’ve always said, if you want to know what RA is really like, ask some one who has it, for goodness sake don’t ask a doctor.
I am 53 yo. Started perimenopause symptoms at age 39. Symptoms lead to me having to take hormones and antidepressant. Fast forward to late 40’s and decided to get off the hormones. Last year I decided to get off of my antidepressant. Life was going ok for about a year and then went downhill. I’m usually a very active person but found myself not being my normal active happy self. Was very emotional, impatient, wanted to sleep all the time, pissy, etc. I did notice over the year I was off the meds that I started to have bad joint pain. I chalked the joint pain up to years of playing sports, being active, and aging or from going off my meds. Decided to go back on meds. Feeling better but the joint pain got worse. Got tested for arthritis at Primary and it came back negative. She still referred me to a Rheumo but having to wait about 5 months before getting to see him as there are only 3 in this area. Appointment is in 3 weeks and it can’t get here soon enough. My active quality of life is awful due to the pain. All I want to do is lay down. Now, after reading this, I’m wondering if stopping the antidepressant could have triggered the arthritis? In your research, have you found in correlation between the two?
All AS/ RA friends…. I have cured my AS with glutenfree diet, lots of fruits n vegetables, no sugar n no modified dairy products, enema therapy twice or thrice a week which I do myself at home, 20 mins yoga n 2.5 km treadmill walk 5 days a week. N of course atleast 8 hours sleep daily
It has worked wonders to me.
Good luck to all my friends
Thank you for your information. I have been fairly healthy most of my life. Started having pneumonia. Doctors said it may be pollution. Been on steroids a lot which causes hair loss for me. One month ago I was diagnosed with RA in my right wrist and hand. How come? pops up a lot in my mind. No family history but going through a dramatic divorce the past year. Thank you for educating me.