History of Sinusitis Raises Risk of Incident Rheumatic Disease

Vanessa L. Kronzer, MD

Credit: Mayo Clinic

A preceding history of sinusitis was linked to a 40% increased incidence of multiple rheumatic diseases, including anti-phospholipid syndrome (APS), Sjögren’s disease, seronegative rheumatoid arthritis (RA), and polymyalgia rheumatica (PMR).¹

Among the population-based cohort collected using the Rochester Epidemiology Project (REP), the association between sinusitis and rheumatic diseases was strongest among the 5 to 10 years before disease onset. The increasing burden of sinusitis, as measured by the number of diagnosis codes, exhibited a significant dose-response association with disease.

“These findings point towards a role for sinus inflammation in the presentation, and possibly pathogenesis, of rheumatic disease,” wrote the investigative team led by Vanessa L. Kronzer, MD, Mayo Clinic.²

Respiratory irritants, such as cigarette smoking, have been linked to the development of nearly all autoimmune rheumatic diseases. In prior analyses, Kronzer and colleagues identified an association between upper respiratory tract diseases, including sinusitis, and an increased risk of incident RA.³ In these data, acute sinusitis was associated with a four-fold increased risk of RA in the 5 to 10 years before disease onset.⁴

Despite this link, the association between sinusitis and other rheumatic diseases remains understudied. To assess this knowledge gap, the investigative team performed a case-control study to measure the association between the preceding history of sinusitis, as well as its timing, and the incidence of rheumatic diseases.¹

Using data from the REP, a medical records-linkage system of ≥500,000 residents in Olmsted County, Minnesota, the analysis included adults from the start of the electronic health record in January 1995 until its last update in December 2014. Investigators restricted the analysis to individuals with ≥7 years of EHR data before the index date of rheumatic disease criteria or matched date for controls.

A total of 1729 adults with newly diagnosed systemic autoimmune rheumatic disease (RA, APS) or vasculitis (PMR) and 5187 matched controls with no rheumatic disease were in the analysis. These individuals were 67% women, with a mean age of 63 years and a median EHR history duration of 14 years.

Upon multivariable analysis, a history of sinusitis was associated with an increased risk for any incident rheumatic disease (odds ratio [OR], 1.4; 95% CI, 1.2 to 17). The association was strongest for systemic autoimmune rheumatic disease, including APS (OR, 7.0; 95% CI, 1.8 to 2.7) and Sjögren’s disease (OR, 2.4; 95% CI, 1.1 to 5.3), and was also identified in PMR (OR, 1.4; 95% CI, 1.0 to 2.0). A strong association was also noted between a history of acute sinusitis and seronegative RA (OR, 1.8; 95% CI, 1.1 to 3.1).

Assessment of the association by the timing of sinusitis revealed the strongest point estimates in the 5 to 10 years before the onset of rheumatic disease (OR, 1.7; 95% CI, 1.3 to 2.3). The strong association was particularly apparent for Sjögren’s disease (OR, 3.2; 95% CI, 1.1 to 9.5) and PMR (OR, 2.0; 95% CI, 1.3 to 3.2).

Moreover, investigators found an increasing burden of sinusitis, as determined by the number of sinusitis codes, had a statistically significant dose-response association with the incidence of rheumatic disease. Those with ≥7 codes for sinusitis exhibited the strongest elevated risk for incident systemic autoimmune rheumatic disease (OR, 1.7; 95% CI, 1.3 to 2.4).

The final key finding revealed the association between sinusitis and incident rheumatic disease was strongest among never-smokers (OR, 1.7; 95% CI, 1.3 to 2.2), compared with ever-smokers (OR, 1.2; 95% CI, 1.0 to 1.6); however, this difference was not statistically significant (P = .06).

Kronzer and colleagues suggested this finding may have been chance alone, given the lack of significance in the p-value. However, they noted a biological explanation could be both smoking and sinusitis provide a similar, thus redundant, inflammatory trigger for disease.

“If true, the strong association between sinusitis and rheumatic disease among never smokers will become more relevant as smoking rates continue to decline,” investigators wrote.

References

1. _{Kronzer VL, Davis JM, Hanson AC, et al. Association between sinusitis and incident rheumatic diseases: a population-based study. RMD Open 2024;10:e003622. doi:10.1136/ rmdopen-2023-003622}
2. _{Sinusitis linked to 40% heightened risk of rheumatic disease (2024) EurekAlert. Available at: https://www.eurekalert.org/news-releases/1035463 (Accessed: 27 February 2024).}
3. _{Kronzer VL, Huang W, Zaccardelli A, et al. Association of sinusitis and upper respiratory tract diseases with incident rheumatoid arthritis: A case-control study. J Rheumatol 2022;49:358–64.}
4. _{Kronzer VL, Huang W, Crowson CS, et al. Timing of sinusitis and other respiratory tract diseases and risk of rheumatoid arthritis. Semin Arthritis Rheum 2022;52:S0049-0172(21)00229-8:151937.}