Male VA Patients Tend to Have More Severe Cases
In 2007 in Fallujah, Iraq, a Marine watches over civilian firefighters at a burn pit as smoke and flames rise into the night sky behind him. Marine photo by Cpl. Samuel D. Corum
Not only does the VA have an unusually high percentage of male patients with rheumatoid arthritis but their cases often are inexplicably severe .Preliminary research might eventually be able to explain why that is the case. New findings have suggested that military burn pit and military waste disposal exposures are associated with rheumatoid arthritis autoantibody expression, and, therefore, might affect the risk of developing rheumatoid arthritis and, possibly, the course of the disease.
LINCOLN, NE — The severity of rheumatoid arthritis among VA patients always has been somewhat of a mystery. The cohort is unusual in some ways—the vast majority of veterans with RA are men—but typical in others, with risk factors such as cigarette smoking highly prevalent.
Now, new research is focusing on a possible explanation: Military burn pit and military waste disposal exposures were found to be associated with rheumatoid arthritis autoantibody expression, and, therefore, might affect the risk of developing rheumatoid arthritis and, possibly, the course of the disease.
Background information in a recent study published in the journal Arthritis & Rheumatology pointed out that RA is three to four times more common in women than men, and that, generally, the VA’s increased focus on the disease appears to be tied by growing numbers of women veterans.
Yet, according to University of Nebraska Medical Center-led researchers, men with RA, including those at the VA, tend to have more severe disease course than women and are more likely to have extra-articular manifestations which contribute to worse outcomes.
While some of the severity might be explained by complicating comorbid conditions, such as cardiovascular disease, data from predominantly male RA cohorts have been scarce, they added.
That’s why the study team sought to determine the association between inhalant exposures with rheumatoid arthritis-related autoantibodies and severity in U.S. veterans. “What we inhale from our environment may affect our risk of developing rheumatoid arthritis by stimulating our immune system to produce pathogenic antibodies,” explained Bryant England, MD, PhD, assistant professor in the UNMC Department of Internal Medicine-Division of Rheumatology & Immunology and Omaha VAMC. “Among the most important findings was the association between military burn pits and waste disposal exposures with rheumatoid arthritis. Autoantibodies were strongest in individuals who also had a genetic background that predisposes them to rheumatoid arthritis-related autoimmunity.”
England, the study’s senior author, suggested that the findings bolster the concept that both genetic and environmental factors drive rheumatoid arthritis-autoimmunity and rheumatoid arthritis risk. He pointed to other emerging evidence that various inhalant exposures influence autoantibody expression and rheumatoid arthritis risk.
For the study, participants in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were mailed surveys assessing occupational, agricultural and military inhalant exposures. Also obtained from the VARA registry were demographic characteristics, disease activity, functional status and extraarticular features, while HLA–DRB1 shared epitope (SE) status, anticyclic citrullinated peptide (anti‐CCP) antibodies and rheumatoid factor (RF) were measured using banked DNA/serum from enrollment.
Researchers assessed associations between inhalant exposures and RA‐related factors, including autoantibodies, severity and extraarticular features.
About half, 50.9%, of participants returned questionnaires. Survey respondents were determined to be older, more often white or male, and less frequently smokers. They also had lower disease activity compared to nonrespondents.
Results indicated that anti‐CCP positivity was more common among veterans exposed to burn pits (OR 1.66 [95% CI 1.02, 2.69]) and military waste disposal (OR 1.74 [95% CI 1.04, 2.93]) independent of other factors. Researchers also emphasized that participants who were positive for SE alleles, burn pit exposure (OR 5.69 [95% CI 2.73, 11.87]) and military waste disposal exposure (OR 5.05 [95% CI 2.42, 10.54]) also were numerically more strongly associated with anti‐CCP positivity.
The study added that several inhalant exposures were associated with the presence of chronic lung disease but not with the presence of RF or the level of disease activity.
“Military burn pit exposure and military waste disposal exposure were independently associated with the presence of anti‐CCP antibodies in RA patients,” the authors concluded. “These findings are consistent with emerging evidence that various inhalant exposures influence autoantibody expression and RA risk.”
England noted emerging evidence that rheumatoid arthritis-related autoimmunity could occur outside of the joints at mucosal surfaces, including in the lungs.
“While smoking has been recognized as the strongest environmental risk factor for rheumatoid arthritis, it is little understood about how other inhalant exposures may affect rheumatoid arthritis risk,” he pointed out, adding that he hopes that study findings will encourage other researchers to continue to study various inhalants as risk factors for the development of rheumatoid arthritis.
“Ultimately, we hope to uncover mechanisms that may help us treat rheumatoid arthritis and rheumatoid arthritis-related lung disease better and pursue a long-term goal of preventing rheumatoid arthritis and rheumatoid arthritis-related lung disease,” England added.
VAMC researchers from Philadelphia; Salt Lake City; Birmingham, AL; Washington; Dallas; Portland, OR; Seattle and Pittsburgh also were involved in the research. It wasn’t the first study to deal with the topic, however.
In 2012, the Department of Deployment Health Research and colleagues from the VA and U.S. military published a study on newly reported lupus and rheumatoid arthritis related to deployment within proximity to an open-air burn pit in Iraq.
In a report in the Journal of Environmental & Occupational Medicine, the authors sought to assess the relationship between possible exposure to smoke from documented open-air burn pits and newly reported lupus and rheumatoid arthritis among Millennium Cohort participants who deployed to Iraq and Afghanistan.
To do that, researchers prospectively assessed self-reported lupus and rheumatoid arthritis among deployers who completed both 2004-2006 and 2007-2008 questionnaires.
After exclusions, the study focused on more than 18,000 participants, more than 3,000 deployed within a 3-mile radius of a documented burn pit. Results of that study determined, however, that proximity within 3 miles of a burn pit was not significantly associated with rheumatoid arthritis or lupus in general, although one location was associated with lupus, but only involved two cases.
The inconsistent association with new-onset RA, notwithstanding, the authors advised that the risk rose among servicemembers whose exposure to burn pits ranged from 132 to 211 days.
The more-recent study noted that exposure to open burn pits in military settings has been linked with a range of lung ailments, including asthma, chronic obstructive pulmonary disease, and bronchitis.
More Focus
The Biden administration has vowed more focus on the toxic effects of burn pits and whether those are behind other medical conditions. The issue is of special importance to President Joe Biden because of the death in 2015 of his son Beau, who was 46. The younger Biden had deployed with the Delaware Army National Guard to Balad Air Base, where the U.S. military burned an estimated 140 tons of waste a day in open-air burn pits.
In a 2019 speech to the Service Employees International Union, Biden said, because of his son’s ”exposure to burn pits, in my view, I can’t prove it yet, he came back with Stage 4 glioblastoma. Eighteen months he lived, knowing he was going to die.”
Advocates who have focused on potential harms from burn pits testified earlier this year at a Senate VA committee meeting that government medical agencies need to view toxic exposure as a high-priority issue deserving of specialized centers for research and monitoring.
They called for Congress or the VA to make a presumptive service connection between some conditions and that veteran’s proximity to toxic substances.
During the last congressional session, bills were introduced in both houses that targeted burn pit exposure and veterans’ benefits. While those did not make it through their various committees before the end of the session, at least one has already been reintroduced this year—The Veterans Burn Pits Exposure Recognition Act. The bill would formally recognize that veterans who served near burn pits in Iraq, Afghanistan and elsewhere were exposed to airborne hazards.
In the recent study on RA and burn pits, the authors wrote, “The independent association of burn pits with chronic lung disease and anti-CCP but not RF, suggests the possibility that this inhalant exposure may induce the generation of citrullinated proteins and inflammatory responses within the lungs, analogous to the pathophysiologic process being identified to accompany cigarette smoking.”
Researchers reported that they found burn pit and military waste exposure to be specifically associated with anti-CCP positivity “in a well characterized cohort of veterans with RA, particularly in those positive for the HLA-DRB1 shared epitope.”
They added, “These findings support emerging evidence that various inhalant exposures may contribute to the generation of RA autoantibodies such as anti-citrullinated protein antibodies.”
- Ebel AV, Lutt G, Poole JA, Thiele GM, et. Al. Association of Agricultural, Occupational, and Military Inhalants With Autoantibodies and Disease Features in US Veterans With Rheumatoid Arthritis. Arthritis Rheumatol. 2021 Mar;73(3):392-400. doi: 10.1002/art.41559. Epub 2021 Jan 29. PMID: 33058561.
- Jones KA, Smith B, Granado NS, Boyko EJ, et. Al. Millennium Cohort Study Team. Newly reported lupus and rheumatoid arthritis in relation to deployment within proximity to a documented open-air burn pit in Iraq. J Occup Environ Med. 2012 Jun;54(6):698-707. doi: 10.1097/JOM.0b013e3182529799. PMID: 22588476.
