I have been asked several times about Mast Cell Activation Disorder (MCAD) by people who think there are red flags that maybe this is a made-up disorder. As I will review below, it is a legitimate and interesting disorder. What is more interesting, from an SBM perspective, is why people would question the diagnosis.

It appears to be a situation of, the quack who cried fake diagnosis. The educated and skeptical public cannot trust apparent experts when they say that a diagnosis is real because there are so many fake diagnoses (and fake experts) out there. This results in real disorders by real experts being doubted because the diagnosis is complex and may share some superficial features with ones that are not real.

Here’s a quick guide to help at least know when to be suspicious of a claimed diagnosis.

Not all diagnoses are created equal

It is first important to understand that medical scientists use different kinds of labels to designate clinical entities. Not everything that is a diagnosis has the same status. The most solid clinical labels refer to pathophysiological diseases. These are clear diseases in which a specific anatomical, infectious or functional pathology has been identified. If you have Type I diabetes, your pancreatic islet cells have been damaged, probably by inflammation, and can no longer produce insulin. Insulin, in turn, has specific effects in the body, mainly transporting glucose into cells so it can be used for energy. A lack of insulin therefore causes increased blood sugar levels while cells are starved for sugar.

Pathophysiological diseases have specific causes and specific effects. They can also generally be diagnosed with objective laboratory tests, and often have specific clinical signs. Our knowledge of specific diseases varies, and some are more heterogeneous than others, but there is no doubt that they are real diseases.

There is also a more fuzzy category of diagnoses, which we may refer to as disorders. The main difference between a disease and a disorder is that we do not understand the pathophysiology. There may not be one specific cause, and therefore there may not be any clear objective test to make the diagnosis. Migraine is a perfect example – there is no doubt it is a real phenomenon, but there is no objective laboratory test to establish it. There is also no one cause for migraine, and the presentation is variable with several subtypes.

Disorders like migraine are usually diagnosed clinically – if you have enough symptoms then you meet the diagnostic criteria. Without clear pathological findings, however, we need to be really careful when establishing such a disorder. Are the symptoms specific or vague? Are there plausible mechanisms? Does the diagnosis predict anything about prognosis or response to treatment?

The third category of diagnostic labels is syndromes. (The term “syndrome” can also refer to a suite of effects from a specific genetic mutation, but that is a different use of the term.) A syndrome is a constellation of symptoms and features that tend to occur together. We don’t even know yet if it is real, if it is one or more disorders, and what the pathophysiology might be. Often such clinical syndromes are just placeholders so that scientists have a common language while researching possible causes and treatments.

We need to be able to discuss and explore syndromes, disorders, and diseases to do research and to treat patients in the absence of definitive knowledge. Problems arise from confusing the different categories – treating a syndrome as if it is a disease, or denying a disorder because we don’t understand the pathophysiology.

Examples along the spectrum

The differences between these categories is perhaps best explained by examples. I have already given diabetes mellitus and migraines as an example of a disease and a disorder respectively. Here are some other common and often controversial diagnoses so we can see where they fit along this spectrum.

Chronic Lyme disease is claimed by some to be a pathophysiological disease, but that designation is premature and probably wrong. The claim is that some people can have a chronic infection with the Lyme spirochete that is reduced by antibiotic treatment but not eliminated. The notion of a chronic infection that cannot be eradicated is plausible, there is just no evidence to support chronic Lyme disease specifically as real. Alleged sufferers do not have any specific signs or symptoms, but rather any of a long list of non-specific symptoms (fatigue, fogginess, achiness, etc.). The diagnosis is largely based on special pleading – atypical clinical syndrome with seronegative tests and an atypical response to treatment. It is essentially Lyme disease without the Lyme disease. The label also doesn’t predict anything, including response to treatment.

Fibromyalgia is a good example of an alleged disorder that is more commonly accepted within mainstream medicine but is also dubious. It is supposed to be a disorder of chronic myofascial pain without a specific identifiable cause. I think fibromyalgia is fine as a placeholder syndrome label. There are patients with chronic myofascial pain without a known cause, and it’s reasonable to give them a syndrome label while we try to sort out what’s going on. The problem is that the label is often used as if it is an established disorder or even disease.

When the diagnostic label was first created it included the criteria that there would be specific trigger points that were especially painful. However, clinicians mostly ignored the trigger points and used the diagnosis as a garbage pail for anyone with unexplained chronic achy pain. So eventually they just dropped the trigger point criterion, now it is officially a garbage pail diagnosis.

Again – such labels are useful, such as “fever of unknown origin” or even “chronic fatigue syndrome” as long as it is understood we are just describing the presentation without making any claims to a specific disease or disorder. Patients with fibromyalgia do not have a specific disease. They have a symptom that needs to be further diagnosed if possible.

Mast cell activation disorder

MCAD, as I stated above, is an actual pathophysiological disease. It is caused by various mutations that alter mast cell function. Mast cells are part of the immune system. They release histamine and other immune mediators. MCAD is often associated with specific skin lesions, which provide a diagnostic sign. It is also possible to measure histamine levels or in some cases identify known mutations.

The reason MCAD may be confused with a dubious diagnosis is that it is very heterogeneous. This is because mast cells exist in every organ in the body and therefore MCAD can have a long list of possible symptoms, depending on the organs involved. In this way it is like lupus, which is a chronic auto-immune disease that can affect any tissue in the body. Also, mast cells release hundreds of immune mediators, and only a small number of them can be measured with commercial lab tests. Further, there are many possible mutations that have not yet been identified.

So it is possible to have MCAD with negative laboratory testing. Still the diagnosis would be based upon some specific findings and does predict response to treatment with antihistamines and mast cell membrane stabilizing drugs.


The whole notion of varying diagnostic labels and our knowledge of specific diseases and disorders is extremely complex, as you might imagine. Unfortunately this means that the situation is ripe for exploitation by charlatans and dubious practitioners. It is easy to make a fake disorder out of non-specific symptoms, and explain away the absence of definitive diagnostic testing, and then prescribe some placebo treatment. When careful scientific testing demonstrates that the alleged syndrome is not real, the charlatans just claim there is a conspiracy, that their suffering patients are being ignored, that mainstream medicine is too closed-minded and in the thrall of the convenient villain of the day. That villain can vary as needed, from Big Pharma, to the insurance industry, to a specific specialty protecting their turf.

The harm from this is extensive. Patients given fake diagnoses are often then given fake, worthless, or even harmful treatments, often at great expense. They are also kept from pursuing their real underlying diagnosis or more practical treatments.

Further, as we see here, the existence of fake experts and fake diagnoses creates a lot of confusion in the general public. They don’t know what to trust and whom to believe. That, I think, is partly the point – to destroy the very nature of expertise. Without legitimate experts, then anything goes. Your snake oil is as legitimate as the best science-based medicine.

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.