Have an MCAS diagnosis? Well, maybe not

Mast cell activation syndrome has gained traction on social – but is it being correctly diagnosed? An MCAS expert explains

1:13 PM

Author | Johanna Younghans Baker

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Justine Ross, Michigan Medicine

If you’ve been struggling with unexplainable symptoms such as chronic fatigue, fibromyalgia, multiple food and environmental intolerances and sensitivities along with negative allergy tests, you may have fallen down the TikTok or Instagram rabbit hole of mast cell activation syndrome.

Many social media posters will definitively report they’ve been diagnosed by a practitioner, or self-diagnosis themselves based on what people post online.

But, in reality, those MCAS diagnoses may be far from accurate.

One of the leading mast cell disorder clinics in the world sits within the allergy division at Michigan Medicine, where many patients get referred to to confirm their diagnosis.

However, an overwhelming amount end up not testing positive, explains Cem Akin, M.D., Ph.D., a world-renowned expert on mast cells who directs the clinic.

“I’d say around 90% of cases that get referred here, which come from all over the country, turn out not to meet MCAS diagnostic criteria. That criteria is established by expert consensus between the United States and European doctors and researchers who spent their careers on studying and publishing on mast cells and the diseases they cause,” said Akin.

And that’s a big problem, he warns.

What is MCAS?

Mast cells are very ancient cells, that, through evolution, have protected humans from harmful stimuli externally and internally.

“They sense something going on. It’s the body’s first alert system,” explained Akin.

Mast cells are in charge of allergic reactions in the body, and their functional roles in maintaining health may include neutralization of toxins and fighting infections.

There are two groups of mast cell disorders: 

  • Primary mast cell disorders in which mast cells are produced abnormally with a mutation causing their proliferation and activation. 

  • Mast cell activation disorders in which mast cells are produced normally, but react to a secondary trigger such as an allergic or inflammatory condition. In some patients, no trigger (mastocytosis, allergic or inflammatory) can be found, which is designated as idiopathic mast cell activation syndrome. 

How is MCAS diagnosed and treated?

In order for doctors to diagnose you with MCAS, you need to have had: 

  • Episodic symptoms in two or more organ systems, known to be caused by mast cell activation 

  • A positive response to treatment with drugs targeting mast cell activation products 

  • An increase in a validated marker known to be released by mast cells during a symptomatic episode.  

A true symptom of mast cell activation syndrome?

Anaphylaxis.

“Someone eats peanut butter, or gets stung by a bee, and they pass out. It’s when someone is extremely allergic to something.”

Then there’s the idiopathic form.

“This is where you get into murky waters and MCAS gets over diagnosed and incorrectly,” explained Akin.

“You can’t find an allergy, and you can’t find the mast cell marker increases, but the patient is still having symptoms.”

For mastocytosis, good pathology criteria exists for testing.

“We know exactly what they look like and how to diagnose.”

But Akin says the idiopathic type of MCAS often gets incorrectly diagnosed because it doesn’t have a clear etiology, and is sometimes used as a diagnosis of exclusion when no other cause is found.

“People assume they developed MCAS from long COVID, or chronic Lyme disease, for instance. They get lumped under mast cell because it may seem similar or have similar symptoms.”

“When we call a disease mast cell activation syndrome, we need to have evidence that the symptoms of the disease are caused, or at least temporally associated with increased mast cell products,” he explained.

Typical symptoms include: 

  • Hives 

  • Flushing 

  • Tachycardia 

  • Diarrhea 

  • Fainting or lightheadedness, occurring in episodes 

However, when patients presents with chronic or less specific symptoms that can be caused by a number of other disorders, the diagnosis become challenging, notes Akin.

The most extensively validated mast cell marker is serum tryptase.

“It is stored in mast cell granules and is released in mast cell activation. It needs to be checked within four hours of symptom onset and compared to baseline levels. Some urine tests such as N-methylhistamine or prostaglandins can also be used but they are less specific than tryptase.”

MCAS diagnosis caution

Akin warns against assuming you have MCAS without a proper medical evaluation, self diagnosing yourself or using the diagnosis as a diagnosis of exclusion.

“It’s dangerous to mislabel patients and call it something when it isn’t. You want to get to the right diagnosis, and that may take time and multiple specialists to assess.”

Akin explains the confusion is also fueled by the presence of alternative diagnostic criteria which maintains a broader symptom profile including less specific symptoms and doesn’t require validated mast cell marker elevations.

Akin emphasizes the need for research to identify and validate more mast cell activation markers that can be used diagnostically and targeted therapeutically.

“My biggest hope is that there’s a cure, and I think we are on the right track for that, and to develop a point of care test that can be used widely,” he explained.

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