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The study aimed to analyze the mortality and leading causes of death associated with Sjögren’s syndrome (SS) in the United States (US) between 1999 and 2020 using a multicause approach. We analyzed mortality based on SS as the cause-of-death. Using mortality rates, number of deaths, and historical trends, we examined sex, age of death, comparisons of SS- and polymyalgia rheumatica-related deaths (multiple cause-of-death) in the last 20 years, changes in the ranking of causes of death when SS was the underlying cause-of-death (UCD) in the first and last 5 years of the last 20 years, and the number of deaths and standardized mortality (per 100,000 people) when SS combined with interstitial lung disease (ILD) or tumor was the multiple cause-of-death. An SS-standardized mortality trend chart and a trend line were created. In 22 years, the total number of SS-related deaths in the US was 7,817, including 7,016 women. When SS was the UCD and non-UCD, the standardized ratios of female-to-male deaths (per 100,000 people) were approximately 4.6–13:1 and 6.8–19.6:1, respectively. SS-related deaths were more common in people aged &gt;60 years and concentrated in patients aged 60–79. In cases where SS and polymyalgia rheumatica were the multiple cause-of-death, the number of deaths and age-standardized mortality of SS and polymyalgia rheumatica increased, although lower in SS than in polymyalgia rheumatica. Regarding SS as the UCD, heart disease ranks first. Concerning the number of deaths and standardized mortality in the first (1999–2003) and second (2016–2020) 5 years, when SS-ILD and SS combined with tumors were the multiple causes of death, the number increased in the second 5 years compared to that in the first 5 years. When SS combined with COVID-19 was the multiple cause-of-death, 73 deaths occurred, comprising 64 females and 9 males. Death predominance was observed among women and patients aged 60–79 years with SS. Although the SS-standardized mortality rate was low, an increasing trend was observed. When SS was the primary cause-of-death, heart disease remained primarily involved, followed by malignant neoplasms. The number of patients with SS-ILD and SS combined with tumors in the past 22 years and the standardized mortality rate after 5 years increased compared with those of the previous 5 years. Concurrent SS and COVID-19 may be related to the increased SS deaths.

Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study