: The prevention of chronic damage, especially in early disease phases, remains an unmet need in the management of Systemic Lupus Erythematous (SLE) patients, despite the application of a so-called treat-to-target strategy. The high proportion of SLE patients developing chronic damage suggests a multifactorial aetiology. Thus, besides disease activity, other factors may contribute to the development of damage. The revision of data published so far underlines that, next to disease activity, it is possible to identify other factors playing a relevant role in damage development and progression. In summary, the presence of antiphospholipid antibodies and drugs used to treat SLE patients, in particular glucocorticoids, is strongly associated with SLE-related damage. Furthermore, recent data suggests the possible role of genetic background in determining the development of specific organ damage, in particular renal and neurological. Nonetheless, demographic factors, such as age, sex and disease duration could exert a role along with the presence of comorbidities. The contribution of different factors in determining damage development suggests the need for new outcomes to assess a comprehensive disease control including not only the assessment of disease activity, but also the evaluation of chronic damage development.
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