In the largest study of diverse RDs, we examined the HRQL of individuals with RD in the U.S. compared to the general population and individuals with common chronic illnesses. Findings were remarkably consistent: compared to both sets of norms, our main sample of persons with RD as a whole scored consistently poorer on every subscale, and those scores were clinically important differences for all but one scale (ability to participate in social roles and activities). Although it is well documented that individuals with common chronic diseases experience challenges to HRQL [6], our findings show that, as predicted, the experience of living with RD leads to even greater HRQL threat. RDs come with a number of unique challenges including accessing diagnoses, medical information, treatment, psychosocial support, and coping with stigma and uncertainty [3, 9, 11].

Intercorrelations revealed interesting patterns. Women experienced poorer HRQL than men. Older participants showed a somewhat paradoxical pattern of poorer physical function yet lower anxiety, depression, fatigue, and pain, which has been found in other chronic disorders [27, 28]. This may be attributed to the notion that physical function limitations are more expected in older age and may result in less distress than when the occur in younger individuals [28]. Interestingly, having symptoms of one’s disease longer was associated with poorer HRQL, but having had one’s diagnosis for longer was associated with better HRQL. Participants in our sample experienced long diagnostic delays, averaging 9 years. This pattern of findings suggests that, although experiencing symptoms for an extended period of time is a risk factor for poor HRQL, receiving a diagnosis is a gateway to treatment and support that can, over time, alleviate some of the HRQL challenges of having a RD. People navigating more than one RD experienced poorer HRQL, suggesting that RDs have an additive effect. People with higher income experienced better HRQL in all domains. People with higher HRQL are more likely to be employed, generate income, have private insurance, and access quality healthcare. Higher income also affords the ability to travel greater distances to seek expert care and support.

Examining specific RD categories, participants with systemic and rheumatic diseases had the poorest HRQL profile, with the worst scores on every domain and scores at least one SD worse than the norm on every scale. Neurological diseases were also characterized by very poor HQRL, with poor physical function, fatigue, and ability to participate in social roles and activities (all greater than 1 SD from the norm). Poor HRQL was also found in immune diseases, including fatigue and pain scores (1 SD from the norm). Participants with neoplastic diseases did not show an extreme pattern of HRQL deficits, with no scores 1 SD or greater from the norm.

Participants with developmental anomalies experienced fewer HRQL deficits than the other categories. In fact, they did not differ from the general U.S. population in ability to participate in social roles and activities, and they did not differ from common chronic diseases in most domains. These findings may be in line with previous research which has found that people with congenital or early onset disabilities and RDs are better adapted and have better disability self-efficacy than those with acquired conditions [29]. Persons with congenital or early onset RDs have had a long time to adapt, and went through their cognitive, physical, and social development with their RD conditions [29]. Thus, they may not experience a functional loss and are less likely to have experienced a change in identity [29].

Our study is noteworthy for its large, diverse sample of people with RDs and use of PROMIS to make comparisons to representative population norms. However, our findings should be considered in light of certain methodological limitations. As with most RD research, it is not possible to determine the representativeness of our sample because there is little research on the demographics of people living with RD [8]. Further, the U.S. does not track diagnoses of most RDs [1], so it is not possible to assess whether certain RDs were over- or under- represented in our sample. For this reason, RD prevalence estimates may change and categorization of diseases as rare or not may change over time. Additionally, our sample had higher income than the general U.S. population. As higher income is associated with higher quality of life in our sample and others [30], and the population of people with RD may be less connected to RD networks and have lower income than our sample, it stands to reason that the population of people with RD as a whole may have even poorer HRQL than our results indicate. It should be noted that the second largest study of individuals with diverse RDs (n = 810), which was conducted in Australia using similar sampling and data collection methods, had a number of similar demographics: a high number of people living with multiple RDs (16%), a high number of neurological RDs, about three quarters of their sample was female, and the majority were middle-aged.

Another consideration is the heterogeneity in RD experiences that may result from our efforts to sample diverse RDs. For example, a participant with cutaneous T cell lymphoma who is relapsing would likely have poorer HRQL than someone who is in remission. That participants scored, on average, significantly poorer in HRQL compared to non-RD samples despite this heterogeneity, strengthens our conclusion that people with RDs as a whole are at greater risk of HRQL problems. This suggests that even people with mild or remitting symptoms need more support than those with common diseases. The final limitation is that Orphanet acknowledges that their linearization rules for categorizing diseases are sometimes somewhat arbitrary [24]. For example, according to their rules, endocrine tumors are classified as rare neoplasms rather than endocrine disease, even though the RD has features of both categories [24]. For this reason, nuances between RDs and categories may have been missed.