Sunday, June 29, 2014

Case Reports of Rare Diseases Have General Value

The Case Report (also known as Case Study) is a poorly utilized resource. Every healthcare worker is familiar with case reports; medical journals sometimes contain a section devoted to them. Case reports typically begin with a comment regarding the extreme rarity of the featured disease. You can expect to see phrases such as "fewer than a dozen have been reported in the literature" or "the authors have encountered no other cases of this lesion," or such and such a finding makes this lesion particularly uncommon and difficult to diagnose; and so on. The point that the authors are trying to convey is that the case report is worthy of publication specifically because it is rare. After describing the clinical and pathologic features of the case, there is usually some obligatory paragraph explaining how the disease can be distinguished from more common diseases, with which it may have overlapping clinical or pathological features. Sometimes the case report will contain an end-paragraph that undermines the accuracy of the start-paragraph, suggesting that the lesion is more common than one might think; implying here that under-diagnosis is the root cause of the lesion's apparent rarity. Always, the case report serves as a cautionary exercise, intended to ward against misdiagnosis.

The "beware this lesion" approach to case reporting can easily miss the most important aspect of this type of publication. Science, and most aspects of human understanding, involve generalizing from the specific. When Isaac Newton saw an apple falling, he was not thinking that he could write a case report about how he once saw an apple drop, thus warning others not to stand under apple trees lest a rare apple might thump them upon the head. Newton generalized from the apple to all objects, and questioned the basic nature of gravity, to produce mathematically-described laws by which gravity interacts with matter.

Every case report of a rare disease or of a rare presentation of a common disease should serve as a special instance of a general phenomenon. In natural systems, there are no outliers. Every event, no matter how rare, is produced as the consequence of general laws of nature. The case report gives us an opportunity to clarify the general way things work, by isolating one specific and rarely observed factor.

Here is an example.

The common heart attack is caused by atherosclerotic plaque blocking a coronary artery. Many conditions produce atherosclerotic plaque, but a rare condition known as familial hypercholesterolemia is associated with some cases of coronary atherosclerosis that occur in young individuals. Studies on familial hypercholesterolemia led to the finding that statins inhibit the rate-limiting enzyme in cholesterol synthesis (hydroxymethylglutaryl coenzyme A), thus reducing the blood levels of cholesterol and blocking the formation of plaque. The treatment of a pathway operative in a rare form of hypercholesterolemia has become the most effective treatment for commonly occurring forms of hypercholesterolemia, and a mainstay in the prevention of the common heart attack.

In this case, the rare instances of inherited hypercholesterolemia clarified the general pathway leading to atherogenesis. Yes, when first encountered, inherited hypercholesterolemia is just the kind of disease that might have appeared as a case report. It would have been a terrible injustice for such a case to be treated merely as a curiosity of medicine or as a cautionary tale for medical students.

The process by which observations on rare diseases can be applied generally to all diseases, is discussed in detail in my recently published book, Rare Diseases and Orphan Drugs: Keys to Understanding and Treating the Common Diseases. The book builds the argument that our best chance of curing the common diseases will come from studying and curing the rare diseases.

I urge you to read more about this book. There's a good preview of the book at the Google Books site.

- Jules J. Berman, Ph.D., M.D.

tags: case report, case study, rare diseases, orphan diseases, orphan drugs, generalizing from rare to common, what is the purpose of case reports, case reporting, case studies, heart attack, heart disease, cholesterol