Have you ever heard of heavy leg syndrome? I hadn’t, until I read this BBC article about it – the British are apparently amused at this peculiarly French medical malady. Heavy leg syndrome is a common diagnosis in France, which alone consumes one third of the world’s drugs for this diagnosis.

Diseases certainly vary from population to population based upon genetics, environment, and lifestyle. But can it also vary just based upon the culture of diagnosis? It seems so.

Ever since it was recognized that there exists diseases – that different people can suffer from the same entity, rather than everyone having their own unique illness, the medical profession has described certain clinical presentations as syndromes. This is legitimate, but it must be recognized that this use of the term syndrome is purely descriptive. (As an aside, the term “syndrome” has a different and very specific use in describing certain genetic diseases.)

Problems arise, however, when syndromes are created too casually.  I always tend to view with suspicion a syndrome that is merely a symptom, especially a common symptom. Is the symptom of heavy legs really heavy leg syndrome?

The sensation that one’s legs are heavy could be a manifestation of leg weakness, in which case the real diagnosis is weakness, which itself can have many possible causes that need to be investigated. Perhaps the leg heaviness is just fatigue (a lack of energy or endurance, whereas weakness is a loss of strength or power).  This in turn can be a symptom of chronic venous insufficiency, in which case that is the actual diagnosis.

Therefore, turning a symptom into a diagnosis can be misleading. It might distract from the proper diagnostic process of finding the true underlying diagnosis that is causing the symptom.

It is also possible that common knowledge of a symptom-based “syndrome” in a culture could lead to its overdiagnosis. Having an official-sounding diagnosis like “heavy leg syndrome” likely promotes confirmation bias. People with vague or nonspecific symptoms hearing about the syndrome are likely to fit their own symptoms to what is described. Clinicians see this all the time – patients come in having read about a disease or syndrome on the internet and they think it fits their symptoms exactly. In reality, the diagnosis does not fit them at all. They are focusing on superficial similarities to their symptoms (“Hey, I feel tired”) and ignore or overlook major inconsistencies or factors that would rule out the diagnosis.

Clinicians too can fall prey to confirmation bias. If we are thinking about heavy leg syndrome we will ask questions of patients that probe for the diagnosis. “Do your legs feel tired? Hmmm…you may have heavy leg syndrome.” It is easy to overestimate the significance of a patient confirming a symptom or finding, without properly considering what the predictive value of that finding is. For example, you may not ask patients in whom you do not suspect the diagnosis if they also have the symptom. Perhaps most people will validate the symptom of tired legs when asked. What does it really mean?

It it therefore extremely easy for both patients and doctors to be firmly convinced in a diagnosis that does not really exist. This confirmation bias feedback loop explains why some diagnoses seem to be so culturally dependent. It also can account for the existence of fake diagnoses favored by some unconventional practitioners.

I also feel that sometimes the casual use of the term “syndrome” to refer to a symptom may encourage a clinician to prematurely give up on the diagnostic process. I have seen this in my clinic, where patients are given a symptom-based syndrome diagnosis when in fact they have an undiagnosed underlying disease. Perhaps that chronic fatigue syndrome is really multiple sclerosis.

All of this is not to say that syndromes cannot be a legitimate part of clinical thinking. They are.  A syndrome is a description of a recognizable pattern that presents clinically in different patients. The presumption is that different people presenting with the same or very similar array of signs or symptoms likely have the same or similar underlying cause. This then creates a starting point for researching the epidemiology, natural history, and ultimately the cause of the syndrome – in which case it may graduate to a disease.

Meanwhile, it is reasonable to treat syndromes and to try to standardize their diagnosis. Patients cannot wait for science to figure everything out about a disease before being treated. Syndromes can be treated by addressing the symptoms, removing exacerbating factors, avoiding risk factors, and making lifestyle changes that improve or compensate for impaired function.

How do we know which syndromes are real discrete entities for which we simply have not yet discovered the underlying cause, and which ones are illusions of confirmation bias? That is the 64 thousand dollar question. Here are some likely guidelines.

Syndromes that have a very specific sign or symptom, or set of signs and symptoms, are more likely to be real unique clinical entities. If a syndrome is associated with the nose turning bright blue, and no other disease is known to do that, then it is very likely that “blue nose syndrome” is a real entity. If, however, a syndrome is merely a single or collection of vague or extremely common and non-specific symptoms,  that syndrome is highly suspect.

If there are biological markers of the syndrome, even if they cannot be reliably used to rule in or rule out the diagnosis, that at least suggests there is something biological going on. This can be very tricky, however, as non-specific lab abnormalities can also feed into confirmation bias.

If a syndrome is seen in many different cultures that too lends to its credibility. A syndrome that seems unique to one culture, however, is more suspect. This should reflect more than naming convention, which is always cultural. For example, the mysterious penis shrinking syndrome is uniquely Asian. It is not known by any name in the West.

Let us consider chronic fatigue syndrome, for example. At its core this is based upon a single non-specific symptom – fatigue.  This is the primary weakness of this syndrome as a diagnosis, in my opinion.

However, the diagnostic criteria for CFS is actually quite rigorous. It requires the existence of other symptoms like muscle pain and chronic infections. It also requires the extensive elimination of any other diagnosis that can explain the symptoms. This is often the mistake that is made – settling prematurely on the diagnosis of CFS without meeting the diagnostic criteria by ruling out other causes, and there are many. There are also biomarkers for CFS, although nothing that can establish the diagnosis.

One possibility is that CFS is actually an immune system disorder and the chronic fatigue is really a manifestation of chronic infections. If this is true, then I think it would be better to come up with a different name for the immune disorder, and recognize that chronic fatigue is just one symptom of this immune disorder, as it is a symptom of many other chronic illnesses. This would avoid much of the confusion generated by the term CFS, and actually make the diagnosis less controversial than it currently is.

Similar controversy surrounds other symptom-based syndromes, like irritable bowel syndrome. There is reasonable evidence that a unique disorder is hiding inside this diagnosis, but it also appears that many people with anxiety or other primary disorders manifest with IBS symptoms. This makes IBS very fuzzy around the edges.

By contrast, restless leg syndrome (RLS) is a legitimate disorder with a fairly specific presentation. Contrary to recent accusations, it was not invented by Big Pharma, it has actually been described in the neurological literature for more than 60 years and is a sufficiently discrete clinical syndrome to warrant its own designation. Its reputation has suffered, however, by the dilution of the term “syndrome” in recent years.

While syndromes in general are legitimate, and in fact are an important part of medicine, the rapid and casual labeling of every nonspecific symptom as its own syndrome can be very counter-productive.  In many cases we can just go back to referring to symptoms as symptoms – which recognizes that there is one or more underlying causes yet to be identified.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the president and co-founder of the New England Skeptical Society, the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also contributes every Sunday to The Rogues Gallery, the official blog of the SGU.