Sinusitis Tied to Later Autoimmune Disease

A history of sinus congestion and drip may be a precursor to serious autoimmune disorders, a population-based study suggested.

Rates of rheumatologic conditions including antiphospholipid syndrome and Sjögren’s disease were significantly higher in people with any experience with sinusitis, with odds up to seven times greater than in individuals with no such history, according to Vanessa Kronzer, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.

For rheumatic diseases of any type, odds were increased 40% (OR 1.4, 95% CI 1.2-1.7) for those with a history of either acute or persistent sinusitis, the researchers reported in RMD Open.

Associations with specific rheumatic diseases were spotty, however. For ankylosing spondylitis, psoriatic arthritis, and most forms of vasculitis and rheumatoid arthritis (RA), only nonsignificant trends toward higher risk were found. And systemic lupus erythematosus trended in the opposite direction, with an odds ratio of 0.5 (95% CI 0.1-1.8).

As that broad confidence interval suggests, rates of many rheumatic disorders may have been too low to detect a real signal, despite more than 500,000 individuals being included in the study. Still, the authors felt the significant associations they did find are clinically relevant. “Overall, these findings point towards a role for sinus inflammation in the presentation, and possibly pathogenesis, of rheumatic disease,” they concluded.

Why look for such an association? Kronzer and colleagues noted that previous studies had identified chronic exposure to “respiratory irritants,” including tobacco smoke, airborne silica, and others as risk factors for various autoimmune diseases. Moreover, their own work had linked a suite of respiratory diseases (including sinusitis) with risk for RA. That led to the question of whether sinusitis by itself — a relatively mild but very common condition — might predispose toward rheumatic disease.

For the new study, the researchers drew on the long-running Rochester Epidemiology Project, with participation from most healthcare institutions in Olmsted County, Minnesota, the region surrounding the Mayo Clinic’s headquarters. Detailed longitudinal data from more than half a million county residents were included.

Kronzer and colleagues focused on individuals with at least 7 years of medical history. They identified 1,729 people with incident rheumatic disease, with their “index date” counted as the first time their records indicated a rheumatic disease diagnosis. Each case was matched with three other people in the database for age at index date, sex, and approximate duration of medical records; 5,187 in total. Participants were counted as having a history of sinusitis if their records indicated such a diagnosis (with the relevant ICD-9 code) at least 1 year prior to their index date.

Only a few dozen people developed rheumatic disease in most categories. For example, there were just 22 cases of ankylosing spondylitis and 26 of antiphospholipid syndrome. The most common disease was RA, of which 688 cases were recorded.

A total of 48 potential associations were evaluated. For some diseases, certain subtypes were examined separately, such as seropositive versus seronegative RA; the researchers also looked for associations with acute versus chronic sinusitis.

Most of these 48 evaluations didn’t reach statistical significance. The strongest link was for antiphospholipid syndrome, which, despite the small number of cases, produced an odds ratio of 7.0 (95% CI 1.8-27) for any type of previous sinusitis and 6.0 (95% CI 1.5-24) in relation to chronic sinusitis. Others included the following:

• Seronegative RA: OR 1.8 (95% CI 1.1-3.1) for acute sinusitis only
• Sjögren’s syndrome: OR 2.4 (95% CI 1.1-5.3) for all sinusitis
• Vasculitis of any type: OR 1.4 (95% CI 1.1-1.9) for all sinusitis, 1.6 (95% CI 1.1-2.2) for chronic sinusitis
• Polymyalgia rheumatica: OR 1.4 (95% CI 1.0-2.0) for all sinusitis, 1.5 (95% CI 1.1-2.2) for chronic sinusitis

Also significant was the association for all cases of systemic disease in aggregate (including Sjögren’s, antiphospholipid syndrome, lupus, and systemic sclerosis), with odds ratios of 2.2 for all sinusitis and 2.6 for chronic sinusitis. Acute sinusitis seemed very weak as a predictor of rheumatic diseases.

Of particular interest, the authors said, was that the associations were strongest when sinusitis occurred 5 to 10 years prior to first diagnosis of rheumatic disease.

Kronzer and colleagues speculated that these associations stem from infections, probably bacterial, that trigger both the sinusitis and the development of autoimmune reactions. They cited earlier studies indicating that “both Staphylococcus and more recently Corynebacterium were implicated in pathogenesis of ANCA-associated vasculitis, whereas Ruminococcus gnavus was associated with lupus nephritis, RA, and spondyloarthritis.” The researchers also argued that this is consistent with the 5- to 10-year delay between sinusitis and rheumatic disease diagnosis, insofar as autoimmune pathology is usually detectable long before clinical symptoms become established.

“Therefore, future studies should replicate the observed association between sinusitis and rheumatic diseases, search for additional causative organisms, and determine whether preventing or treating sinusitis can prevent and/or treat rheumatic diseases,” Kronzer and colleagues wrote.

Limitations to the study included the small number of incident rheumatic disease cases in the database, the reliance on administrative data, and the geographically and sociodemographically restricted sample. The researchers also acknowledged the potential for reverse causation, in which the presence of subclinical autoimmune disease might promote sinusitis. Unmeasured confounders could have been present as well.

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