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Background Systemic autoimmune diseases (SAIDs) have chronic trajectories and share characteristics of self-directed inflammation and aspects of clinical expression. Nonetheless, burden-of-disease studies rarely investigate them as a distinct category. This study aims to assess the mortality rate of SAIDs as a group and to evaluate co-occurring causes of death. Methods We used death certificate data in the Netherlands, 2013-2017, (N = 711,247) and constructed a SAIDs list (4-position ICD-10). The mortality rate of SAIDs as underlying Cause of Death (CoD), non-underlying CoD, and any-mention CoD was calculated. We estimated age-sex-standardized observed/expected ratios to assess comorbidities in deaths with SAID relative to the general deceased population. Results We observed 3,335 deaths with SAID on their death certificate (0.47% of all deaths). The mortality rate of SAID was 14.6 per million population as underlying CoD, 28.0 as non-underlying CoD, and 39.7 as any-mention CoD. The mortality rate was higher for females and increased exponentially with age. SAID-related deaths were positively associated with all comorbidities except for solid neoplasms and mental conditions. Particularly strong was the association with musculoskeletal (O/E=3.38,95% CI[2.98,3.82]), other genitourinary (O/E=2.73,95% CI[2.18,3.38]), blood (O/E=2.02,95% CI[1.70,2.39]), skin and subcutaneous tissue (O/E=1.95,95% CI[1.54,2.45]), and infectious diseases (O/E=1.85,95% CI[1.70,2.01]), as well as influenza (O/E=2.71,95% CI[1.74,4.03]). Conclusions Systemic autoimmune diseases constitute a rare group of causes of death, but contribute to mortality through multiple comorbidities. Classification systems could be adapted to better encompass these diseases as a category. Key messages Reclassification of readily available data provides useful estimates for the mortality burden of systemic autoimmune diseases in the population.

531Investigating systemic autoimmune diseases as a group of causes of death: mortality burden and comorbidities