What constitutes a “rare” disease, and why is this consideration important?

The definition of “rare” disease differs from country to country, but generally, a rare disease is one that is diagnosed only in a small minority of individuals; these diseases are low on any physician’s list of differential diagnoses and do not take up the bulk of medical resources. 

The manner in which doctors learn about various pathologies typically follows a stepwise approach: the most common diseases are ranked first—these are diseases that doctors are most likely to come across and thus should not be missed; next are diseases that are less common—in an entire year a doctor might see a handful of these cases. On the last rung of the ladder are diseases that are considered “rare”—these are typically diagnosed only after basically all other causes have been ruled out. 

Continue Reading

Defining “Rare” Disease

Let’s take a look at how rare diseases are defined in China, one of the most populous nations in the world. In Intractable & Rare Disease Research, Lu and Han discussed the latest definition of rare disease in China, released in September 2021. 

First, an important caveat. They explain that, “There is no standard definition of rare diseases, it is affected by many factors, such as medical status, the level of social security, social and economic development, and human cognition of the disease.”

The latest definition of what may constitute a rare disease in China is a condition that afflicts less than 1 in 10,000 newborns or fewer than 140,000 individuals. The figure “140,000” was determined based on the Chinese population, which numbers 1.4 billion, meaning that a disease is considered rare if it has a prevalence of 1/10,000. 

China is unique in that it has a definition of rare disease determined by the percentage of newborns affected—many nations only define rare disease by the proportion of the total population diagnosed with a particular condition. This unique approach has its advantages—approximately 80% of rare diseases are genetic, meaning that they can theoretically be diagnosed at the perinatal stage. 

Although the latest definition of rare diseases in China will undoubtedly be useful for epidemiologists and clinicians alike, Lu and Han argue that there are certain gray areas that deserve further clarification. For example, there is debate on whether rare infections or conditions caused by environmental factors should be included in the list of rare diseases. A case in point: hepatitis E qualifies as a rare disease according to the latest Chinese guidelines, but hepatitis B, C, and D do not. 

“The new 2021 definition of rare diseases represents just the tip of the rare disease iceberg,” they concluded. 

Not So Rare After All? 

While the exchange of ideas continues regarding whether certain diseases should be deemed rare for the sake of equitable healthcare resource allocation, another debate goes in the opposite direction: if the prevalence of certain rare diseases increases above a certain threshold, should they still be considered rare at all? 

This is the unique question posed by Pergolizzi Jr. and colleagues in Advances in Therapy. The disease in question is idiopathic pulmonary fibrosis (IPF)—a progressive, irreversible lung disorder that leads to early mortality. 

Read more about IPF etiology

No one knows the exact pathophysiology of IPF, but it has most recently been linked to COVID-19 and other chronic viral infections; these are thought to be risk factors for the development of this disorder. Scientists have also proposed a number of other possible risk factors: cigarette smoking, occupational hazards, and air pollution, among others. 

Interestingly, Pergolizzi Jr. and colleagues point out that IPF is considered a rare disease in every country of the world except for South Korea. For reasons unknown, the prevalence of IPF in South Korea is exceptionally high, especially when compared with nations such as the United States. Of course, this may simply mean that IPF is underdiagnosed in other parts of the world. 

The research team conducted a narrative review to better understand the epidemiology of IPF. They used academic search engines to look up studies related to IPF epidemiology. 

They discovered that the incidence and prevalence of IPF is rising across the globe. There are a number of factors that may be driving this growth. First, better diagnostic tools; second, better awareness; third, individuals now have a longer lifespan, allowing this disease to manifest later in life. 

Read more about IPF epidemiology 

In the United States, a study of the prevalence of IPF among veterans is particularly illuminating. From 2010 to 2019, the prevalence of IPF increased from 276 cases per 100,000 individuals to 725 cases per 100,000 individuals; the annual incidence rose from 73 per 100,000 person-years to 210 cases per 100,000 person-years. This means that cases have more than doubled in the span of a decade. 

“IPF is a rare lung disorder that may not be rare much longer; incidence and prevalence are increasing around the world, although the reasons for this are not entirely clear,” the authors concluded. 

It is clear that the definition of what constitutes a rare disease needs to be revisited as some diseases become less common and others become more prevalent. In the midst of this debate, it is important to ensure that adequate healthcare resources are made available to treat patients in any disease category, regardless of their rarity status. 


Lu Y, Han J. The definition of rare disease in China and its prospectsIntractable Rare Dis Res. 2022;11(1):29-30. doi:10.5582/irdr.2022.01034

Pergolizzi Jr JV, LeQuang JA, Varrassi M, Breve F, Magnusson P, Varrassi G. What do we need to know about rising rates of idiopathic pulmonary fibrosis? A narrative review and updateAdv Ther. 2023;1-13. doi:10.1007/s12325-022-02395-9