OBJECTIVES: Systemic sclerosis (SSc) is a rare autoimmune disease with multiple disease manifestations. This structured literature review aims to identify the additional mortality risk, and the humanistic (health-related quality of life [HRQoL]) and economic burden of eight manifestations: interstitial lung disease and/or pulmonary hypertension, and cardiac, renal, gastrointestinal, musculoskeletal, peripheral vascular, and skin manifestations.

METHODS: Electronic databases (Embase, MEDLINE, PubMed, and NHS Economic Evaluation Database) were searched and supplemented with manual searching. Studies published between 2018-2023 reporting SSc organ manifestation impact on survival or evaluating HRQoL, healthcare resource use or cost impact compared to SSc patients without the manifestation were included. Meta-analyses with no publication limits were also included.

RESULTS: Fifty studies were included: 37 reporting mortality outcomes, 9 reporting humanistic burden, and 11 reporting economic burden. Pulmonary, cardiac, and renal manifestations were generally associated with a higher mortality risk compared with SSc patients without manifestations. Multivariate Cox regression analyses and meta-analyses estimated that these manifestations are associated with an approximately 2 to 4-fold increased risk of mortality. Gastrointestinal, skin, and peripheral vascular manifestations were all reported to be associated with poorer HRQoL outcomes, including reduced physical, mental, and social functioning. Pulmonary manifestations were associated with substantial economic costs. The cost burden of other manifestations is insufficiently reported, despite evidence that they often require healthcare resource use.

CONCLUSIONS: The burden of SSc disease is high, and patients with specific organ manifestations often experience poorer quality of life and may have a significantly higher risk of mortality. The economic burden of many manifestations, including those that are widely experienced by SSc patients such as gastrointestinal issues, is poorly understood. Consequently, there is a need for further high-quality research to quantify the direct and indirect economic burden of these manifestations.