Journal of the European Academy of Dermatology and Venereology | 2021
Epidemiology of rare diseases is important
Abstract
Epidemiology of rare diseases is important Rare diseases are an emerging public health priority in Europe. It has been estimated that there are more than 6000 distinct rare diseases; all organ systems can be affected. More than 70% of rare diseases are genetic and most of them show a chronic course. In the EU, rare diseases are defined as conditions that affect less than 50 persons per 100 000 population. The American orphan drug act from the year of 1983 defined rare diseases as disorders that affect less than 200 000 persons in the country, which at that time corresponded to a prevalence of 86 per 100 000 population. Knowledge of the epidemiology of rare diseases is important for several reasons, including determination of specific needs of patients with rare diseases in the health care systems, better management, or estimation of the numbers of individuals profiting from drug development and novel therapies, or participating in clinical trials. However, the epidemiology is challenging since most studies addressing incidence or prevalence arise from national, often small registries on single diseases or disease groups. High-quality epidemiological data are urgently needed. A recent study by Wakap et al. presented progress in this context. Using the publicly available Orphanet database and its Orphanet epidemiological file, the authors estimated the cumulative point prevalence of rare diseases as a group, not based on single diseases. The population prevalence of rare diseases was estimated to be 3.5%–5.9%, which equates to about 260–440 million individuals affected worldwide at any time. This large figure demonstrates the significance of rare diseases as a group, in particular since there is great unmet medical need in the diagnostics, management and treatment of these disorders. Although the group of rare diseases is heterogeneous, the diseases share common features and challenges, including lack of information, scarcity of expertise, delayed diagnosis, the chronic course of the disease, and no cure. In the context of up to 600 rare skin diseases (https://ernskin.eu/), past studies on the epidemiology of epidermolysis bullosa (EB) have revealed substantial challenges. A dozen or so publications have reported the incidence and/or the prevalence of EB in different countries worldwide (see Ref. [2] and the references therein). A 16-year cross-sectional, longitudinal study in the continental United States with more than 3000 patients indicated an overall incidence of 19.6 per million live births and a prevalence of 11 per 1 million population. Several other national studies reported a prevalence ranging between 4 and 10 per million population, except in Scotland where a five times higher prevalence of 49 per million population was calculated. The comparison of these data has been challenging, since they are variably comprehensive and derived from rather small cohorts. In this issue of The Journal, Baardman et al. report “Novel insights into the epidemiology of epidermolysis bullosa (EB) from the Dutch EB Registry: EB more common than previously assumed?”. This interesting observational study describes a cohort of all EB patients based in Netherlands and captured in the Dutch EB Registry during a 30-year period, from 1988 to 2018. The epidemiological data were calculated on the basis of clinical, morphological and molecular diagnostic data and a longitudinal follow-up of 464 patients. In 90%, the diagnosis was genetically confirmed. The accurate diagnosis is a great advantage compared to previous epidemiological studies, in which the diagnosis was mostly based on clinical or morphological criteria, but was not genetically confirmed. Intriguingly, the Dutch registry study revealed an incidence and a prevalence of EB in the Netherlands that was clearly higher than reported previously. The incidence of EB was 41.3 per million live births and the point prevalence was 22.4 per million population. The higher epidemiological outcomes were presumably based on a high detection rate of individuals with EB in a well-organized national healthcare system and a national centre of expertise. An advantage is that in the Netherlands, a small and highly populated country, there is only one centre of expertise for EB to which most patients are referred. A well-organized collaboration between specialists and the fact that all genetic analysis of EB were performed in the same centre of expertise facilitated the capture of patients in the registry, and it is likely that the registry figures mirror the actual numbers of EB patients in the Netherlands. However, despite all of this, a certain risk of underestimation or also misdiagnosis cannot be excluded. Now the question arises whether the epidemiological outcomes are indeed higher also in other countries, and whether they influence determination of patient needs in the healthcare systems, public health approaches, or estimates on therapy needs in a global setting. In the future, international registry studies will have to validate the worldwide incidence and prevalence of EB and, in analogy, of other rare diseases of the skin. The Dutch study clearly demonstrates the importance of thorough reporting systems and high-quality registries as tools for epidemiological studies. Reliable epidemiological data will not only pave the way for public health approaches, such as defining population impact, examining cost, or planning better management of rare diseases,