Systematic review on rare diseases and work: challenges in understanding social inequality pathways

Abstract Background Poor health can exacerbate social inequalities by limiting individuals' ability to accumulate wealth and sustain employment, contributing to health selection effects. Among younger patients with rare diseases (RDs), these effects may be more pronounced, with long-term consequences for human capital, career development, and income. Building on a review of international literature, this communication highlights the methodological challenges in assessing the work-related consequences of RDs. Methods A systematic literature review was conducted following the PRISMA checklist. PubMed, Embase, and Web of Science were searched (2013-2023) for studies on employment or work ability among individuals with RDs compared to a control group. Results Of 7,694 abstracts screened, 44 studies on 34 RDs met inclusion criteria. Findings consistently indicated a negative impact of RDs on employment outcomes, supporting the presence of health selection effects: 87% of studies reported higher rates of work disability, 90% noted increased absenteeism, and all studies (100%) found greater impairment at work among RD populations. However, the majority relied on medico-administrative data, often excluding pediatric conditions and thereby skewing the representation of RDs. In addition, a lack of longitudinal designs across studies limited the ability to explore reverse causality between health status and employment outcomes. Conclusions Individuals with RDs generally face poorer work-related outcomes. However, current research is constrained by methodological shortcomings, particularly the absence of longitudinal data and underrepresentation of pediatric diseases, which hinder a clear understanding of health selection effects. Future research should prioritize longitudinal designs and more inclusive data sources to better capture the complex, bidirectional relationship between health and employment, and to inform effective policy responses. Key messages • Rare diseases are linked to poor work outcomes, but social mechanisms and biases must be considered. Work ability should be supported by including rare diseases in work policies. • Individuals with rare diseases face work challenges, but research limitations, such as lack of longitudinal data, hinder understanding of the complex link between health and employment outcomes.