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Posted by on May 10, 2013 in The Diagnosis |

The Diagnosis Challenge

The Diagnosis Challenge

Prolonged Diagnostic Limbo

Diagnosing mastocytosis is a very difficult matter.

It is not uncommon for patients to be left in “diagnostic limbo” for decades and being mis-diagnosed several times during their lifetime, before eventually a mast cell disorder is finally declared.

Of course, during these decades, mastocytosis keeps progressing over time and patients are meanwhile being treated for misdiagnosed disorders they do not have, with treatments that obviously fail to cure them.

Here's how Dr. Afrin, a world class expert on mast cell disorders, qualifies the problem:

You will not find another disease besides systemic mast cell disease that better illustrates the old “four blind men and an elephant” problem. There are lots of factors that go into every specialist looking at a patient with mast cell disease from a different perspective, seeing only the problems that they’ve been taught to see in their own domain. And in the first 13 years of my career post-fellowship, I practiced that way, too.

As just one example, I can’t begin to count the numbers of patients I’ve seen in that time who’ve had “anemia of chronic inflammation.” Mysterious anemia, nobody knows why, no clear source of the chronic inflammation, and we just leave it at that.

And it’s acceptable in the medical community to just leave it at that. For lots of reasons (many relating to our healthcare financing systems), the physician can’t spend nearly as much time with each patient as would be needed or desirable to get to the root of every mystery.

So the hematologist sees the anemia, the gastroenterologist sees the irritable bowel syndrome, the rheumatologist sees the fibromyalgia, the cardiologist sees the palpitations, the neurologist sees the migraine headaches and neuropathy, and so on and so forth.

We all just constantly miss the elephant.

Heterogeneity of Symptoms

That's the problem, right there!

You'll often read in the medical literature that mastocytosis presents an “heterogeneity of symptoms”. That means that the symptoms are diverse in kind or nature, composed of diverse parts, or resulting from differing causes.

The symptoms are also contrarian, the same cause having a different effect.

Want examples of the contrarian nature of mastocytosis symptoms? Well, here are a chosen few:

  • Patients can have high blood pressure andlow blood pressure.
  • They can have sweats and colds.
  • They can exhibit too many red blood cells or too few red blood cells.

And the contrarian list goes on and on.

Also, if you stopped by the Symptoms list before arriving here, you now know that the mastocytosis symptoms are all over the place. There are, literally, hundreds of symptoms if you consider their different combinations.

And to make matters worse, the symptoms overlap with similar symptoms of other afflictions.

As if it were not enough, the symptoms presented by mastocytosis patients are very diverse, occur in different episodes throughout the patients life, are waxing-and-waning, repetitive  but not necessarily over a contiguous period of time and varying in intensity. Sometimes, some symptoms will go into complete remission, only to come back after a while.

And lastly, many clinicians are unfamiliar with the disease and thus may fail to consider the diagnosis. Even when mast cell disease is suspected, testing for the condition can be falsely negative as a result of technical problems.

An Extreme Case?

Here is the case of Yasmina Ykelenstam, which you can read on her site

For over 20 years I was the guinea pig of 68 overzealous doctors who attempted to convince me I suffered from: recurrent sinusitis that required surgery, multiple sclerosis, lupus, hepatitis, lyme disease, kidney failure, liver failure, leukemia, ovarian cancer, breast cancer, uterine fibroids, endometriosis, chronic urinary tract infections, bladder cancer, diabetes 1 & 2, STIs, pelvic inflammatory disease, brain tumor, bipolar disorder, generalized anxiety disorder, unipolar depression and borderline personality disorder.

The emergency room became my second home: multiple anaphylactic and heart attack like symptoms, two operations (one of which proved completely unnecessary). I was told I needed another six, which I refused. I grew more alarmed with each negative result, believing for many years that I was in fact dying.

Diagnosed with histamine intolerance (HIT) in 2010, I’ve just recently (in March 2013) been diagnosed with Mast Cell Activation Disorder by Dr Matita (under Dr Luis Escribano) in Toledo, Spain.

This isn’t a progression of my condition, but rather a clarification, as I’m certain that’s what I’ve had all along. I have the anaphylactic episodes to prove it.

Extreme? Perhaps … After all, Yasmina is suffering from MCAS, which is mast cell dysfunction which is even more difficult to diagnose than mastocytosis, because the criteria have not (yet) been set by the WHO, unlike the case for mastocytosis.

But here are some words from Dr. Sibbald, a Canadian expert of mastocytosis:

We did a paper with a professor at the University of Toronto on the many faces of mastocytosis. Often patients are told they’re crazy and go, on average, up to 10 years without a diagnosis.

And here are some remarks from Dr Afrin, which refer to MCAS but equally apply, in my opinion, to mastocytosis:

These patients go through doctors by the trainload.

They accumulate large problem lists, and after they figure out, after about 2-3 years of symptoms, that their symptoms aren't going to kill them, and they've learned that no doctor is going to be able to figure out a diagnosis, they stop reporting their symptoms.

They may well continue to regularly suffer a wide range of symptoms, but they simply stop volunteering such information to the clinicians they see, because such abnormality has become their new normality.

So it really is critical, in trying to clinically detect whether mast cell disease might be present, for the clinician to take the time to take a complete review of systems.

A ‘Rare’ Disease

The trouble is, there are not many doctors who have the necessary expertise, patience or time to go through that complete review.

So, patients are misdiagnosed.

So, mastocytosis is not reported.

So, mastocytosis is still deemed to be a ‘rare' disease.

And, in closing, here's what the Mastocytosis Society Canada says:

Despite mastocytosis & related mast cell disorders being classified as rare, escalation in the prevalence of these patients worldwide has resulted in a flurry of medical research ongoing in numerous countries. This indicates that these disorders may not be rare, but rather have been commonly misidentified and unfortunately for patients worldwide, commonly undiagnosed. Since approximately 2005, every year there are new theories, classifications, and adjustments to the mastocytosis definitions due to escalation of patients presenting with these disorders worldwide.

Yes, I Know …

I did say ‘in closing' on the previous paragraph.

But I thought I would add what, in my opinion, is quite a sober but positive message about living with mastocytosis.

Life is worth living.

Even with mastocytosis.




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Posted by on May 12, 2013 in The Diagnosis |



Mast Cell Activation Symptomatology

Here is an obligatory video on any mastocytosis site. This is a video produced by The Mastocytosis Society, featuring the top world experts, talking about the symptomatology of mastocytosis.

Remember their names! These guys will become you best teachers …


Video Transcript

To follow …


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Posted by on May 12, 2013 in The Diagnosis |

WHO Criteria For Diagnosis

WHO Criteria For Diagnosis

Confused about the diagnosis criteria? Wonder whether you fit in the WHO criteria? Head for the forums in Hello all, It’s me … I’m new here.. board to discuss!

The Need For Criteria-based Diagnosis

As we already know, diagnosing mastocytosis is not an easy task. There are so many diverse, seemingly unrelated symptoms that patients can experience. And with many of these symptoms also being present in other conditions, diagnosing mastocytosis on the basis of its symptoms is virtually impossible.

During several decades of testing and diagnosing patients, some patterns began to emerge. Patients who were eventually diagnosed with mastocytosis presented some commonalities in their test results.

So, in 2001, the World Health Organisation, whose job it is to provide leadership on global health matters, as well as setting medical and clinical norms and standards, came up with a series of criteria which guided physicians into a method for mastocytosis diagnosis which is based on test results. The criteria was further refined by the WHO in 2008, based on new findings since 2001.

The WHO also structured a classification of mastocytosis, defining several different types and states of the disease.

The WHO Criteria For Diagnosing Mastocytosis

There are major and minor criteria to be considered during diagnosis. The importance of the major/minor criteria distinction will become clear in a minute. At this stage, please notice that  the criteria have nothing to do with symptoms.

Let's describe the criteria first:

Major Criteria

  • Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organ(s) (>15 mast cells in aggregate)

Minor Criteria

  1. Mast cells in bone marrow or other extracutaneous organ(s) show an abnormal morphology (> 25%)
  2. c-KIT mutation at codon 816 in extracutaneous organ(s). (Activating mutations at codon 816; in most cases, c-kit D816V)
  3. Mast cells in bone marrow express CD2 and/or CD25
  4. Serum total tryptase > 20 ng/mL (does not count in patients who have associated hematologic clonal non-mast cell lineage disease)

Now, let's review the criteria in a bit more detail:

The major criterium looks at the result of a bone marrow biopsy and/or a biopsy of  other organs (e.g., gastrointestinal tract biopsies, liver, spleen).  And you'll have a pathologist looking at the biopsy slide under a microscope. That poor guy needs to find clusters (dense aggregates) of more than 15 mast cells within the field of view of his microscope. And the pathologist must find such a cluster in more than one place (multifocal) in his FOV.

Now, for the minor criteria:

  1. Twenty five percent of mast cells found by inspecting the biopsy must be oddly (spindly) shaped to score one minor criteria.
  2. If you have read the post What Are Receptors? , you know all you need to know to understand what  minor criteria 2 means: you must exhibit ‘the' c-KIT mutation. Specifically, the one which is called D816V. (But you'll remember c-KIT can mutate in many different forms. Still, the D816V is the one specifically required to score that point.
  3. Criteria 3, about the CD2/CD25 stuff? That means the mast cells found in the biopsy must have two types proteins (called CD2 and CD25) sitting on the cell membrane. Apparently, these two proteins found on the cell surface at the same time is not a good thing. Score one more point if you have these 2 little critters (although research now shows that CD25 is the more important of the two. You could virtually score the point if CD25 was the only one present).
  4. And criteria 4 is easier to understand. Score one more point if your blood test shows that you have double the normal amount of tryptase (20 nanograms per milliliter of blood). BUT don't score that point if you have been diagnosed with a blood cancer of some sort  ( associated hematologic clonal non-mast cell lineage)

Diagnosing systemic mastocytosis by WHO 2008 criteria requires you to either have those clusters of more than 15 mast cells in your biopsies or to have scored 3 points of the minor criteria category.

Now let's focus on the classification of the disease.

 WHO Classification of Mastocytosis

In 2001, the World Health Organization developed a consensus classification system for mastocytosis.

This system separates mastocytosis into cutaneous mastocytosis (CM) and five main subtypes of systemic mastocytosis (SM).

CM is diagnosed by the presence of skin lesions and the absence of definitive systemic (meaning, in organ systems)  involvement by mast cells. It is also known as Urticaria pigmentosa (UP) maculopapular cutaneous mastocytosis (MPCM), diffuse cutaneous mastocytosis (DCM), and solitary mastocytoma.

As for SM, first, we have the form of indolent systemic mastocytosis (ISM), which is the vast majority of patients with SM. As distinct from UP, where no other organs than the skin is involved, SM exhibits  enlarged liver or spleen. The GI tract may also be affected. Mediator-related symptoms are common in SM, but the grade of bone marrow infiltration is low, usually less than 5 percent.

Second, we have the form in which there is a associated hematologic non-mast cell lineage disorder (which basically means a blood cancer of some sort, like lymphoma or leukemia) associated with the mast cell disease (ISM-AHNMD). It is far more often the case that we recognize the lymphoma or leukemia and don’t see the underlying mast cell disease unless it happens to be picked up by chance in a bone marrow biopsy.

Third, we have the subvariant of SM called Smouldering Systemic Mastocytosis (SSM), where mast cells have infiltrated the bone marrow more than 30 percent  and total tryptase levels greater than 200ng/mL. There is also a significant level of organ enlargement (liver, spleen, lymph nodes).

Fourth, aggressive systemic mastocytosis is the form of the disease in which the cells have actually infiltrated into a given organ (for example, the liver) and are causing significant organ dysfunction.

And finally, we have the extremely rare – and, for all intents and purposes, universally rapidly fatal – mast cell leukemia.


If you are new to this, no doubt you will be confused. It takes a while to sink in. Please join us in the forum and ask questions.

Show Me!

Here's a short video by Nancy Gould, recapping the diagnosis criteria in a hi-tech, lo-tech way.

Nancy Gould, a mast cell patient and registered nurse, was also a humanitarian who devoted her life to researching and helping mast cell patients get better. Nancy passed away 12/6/12.



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Posted by on May 12, 2013 in The Diagnosis |

Treatment Approach

Treatment Approach

Puzzled about the difference between Mastocytosis and MCAS? You're not the only one! Please head for the forum to find the answers.

We know that mastocytosis cannot be cured.

That only means we do not have a cure today. But research is progressing, and quite honestly, I have got the feeling that research is speeding up due to the herculean effort of some pioneer doctors and a renewed realisation that there may be more people affected by this disease than originally thought.

Don't quote me on it, that was only my personal feeling.

So, in the meantime, until we collectively (meaning doctors AND patients) find a cure, what the heck do we do to make our lives a bit easier?

There are several things that create the symptoms:

1) Too many mast cells are being produced

2) The mast cells release mediators for the wrong reason

3) Too many mediators everywhere are causing havoc in the tissues, organs, vessels, nerves, you name it …

4) Too high a concentration of mediators

So, if we want to get some semblance of control, here are the things that we can do

  • You can inhibit mediator production, and there are various approaches to doing that.
  • You can inhibit mediator release or stabilize the mast cell, and there are a variety of treatments for doing that.
  • You can block the mediators after they've already been released (for example, with antihistamines).
  • You can try and avoid adding histamine to your system by controlling your diet
  • You can undertake a usually futile effort to try to kill the surplus cells

There is currently no cure for mastocytosis, but there are a number of medicines to help treat the symptoms:

  • Antihistamines block receptors targeted by histamine released from mast cells. Both H1 and H2 blockers may be helpful.
  • Leukotriene antagonists block receptors targeted by leukotrienes released from mast cells.
  • Mast cell stabilizers help prevent mast cells from releasing their chemical contents. Cromolyn sodium oral solution (Gastrocrom / Cromoglicate) is the only medicine specifically approved by the U.S. FDA for the treatment of mastocytosis. Ketotifen is available in Canada and Europe, but is only available in the U.S. as eye drops (Zaditor).
  • Proton pump inhibitors help reduce production of gastric acid, which is often increased in patients with mastocytosis. Excess gastric acid can harm the stomach, esophagus, and small intestine.
  • Epinephrine constricts blood vessels and opens airways to maintain adequate circulation and ventilation when excessive mast cell degranulation has caused anaphylaxis.
  • Salbutamol and other beta-2 agonists open airways that can constrict in the presence of histamine.
  • Corticosteroids can be used topically, inhaled, or systemically to reduce inflammation associated with mastocytosis.
  • Antidepressants are an important and often overlooked tool in the treatment of mastocytosis. Depression and other neurological symptoms have been noted in mastocytosis. Some antidepressants, such as doxepin, are themselves potent antihistamines and can help relieve physical as well as cognitive symptoms.

In rare cases in which mastocytosis is cancerous or associated with a blood disorder, the patient may have to use steroids and/or chemotherapy. The agent imatinib (Glivec or Gleevec) has been found to be effective in certain types of mastocytosis.

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Posted by on May 12, 2013 in The Diagnosis |

Is It Cancer?

Is It Cancer?


Puzzled about the difference between Mastocytosis and Cancer? You're not the only one! Please head for the Why Is It All So Confusing section of the forum.

If you have been diagnosed with matocytosis and you are seeing an oncologist and you are treated in a cancer center, you may wonder …

But let me reassure you, unless you are in the tiniest minority of patients, mastocytosis is not cancer.

Cancer is a case of too much of a bad thing. Mastocytosis is a case of too much of a good thing, so to speak.

Here's what Mastocytosis Society Canada has to say about this:

Cutaneous and Indolent forms of mastocytosis, and mast cell activation disorders, are not cancer.

Some aggressive forms of mastocytosis and mast cell leukemia do involve types of cancer.

In most cases, mastocytosis does not equal cancer.

However, this is a neoplastic disorder which refers to the abnormal proliferation of cells. Cancer is also classified as neoplastic. The difference is that cancer cells are malignant. Mast cells are actually good immune system cells but in the case of mastocytosis and other mast cell disorders, the mast cells may be elevated in numbers and/or behaving abnormally.

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Posted by on May 12, 2013 in The Diagnosis |

Mastocytosis Vs. MCAS

Mastocytosis Vs. MCAS


Puzzled about the difference between Mastocytosis and MCAS? You're not the only one! Please head for the forum to find the answers.

Simplicity At It’s Best

You know, I officially launched this site without having any content in this post. It's just that I had difficulty clearly formulating in my mind the difference between mastocytosis and MCAS. And in particular, since the symptoms of both diseases are so similar, why it mattered that MCAS was diagnosed. Would it not suffice to treat an MCAS patient as is he/she had mastocytosis?

The more I read about the topic, the more I stumbled against “Yes, buts”‘ and “What Ifs”. So the site went live without any detail here.

And then something made me think about Nancy Gould, when I read an article about her life (she died in 2012). And then it occurred to me to check YouTube to see if she'd left a video about the topic.

And sure enough, there it was …

The most cogent, simple and brilliantly explained difference between mastocytosis and MCAS.

I love the way she presented it.

Nancy, you are sorely missed …

Does It Matter Whether You Know Your Correct Diagnosis?

According to Nancy Gould, of course it does !

Watch and enjoy the simplicity of her explanation.



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