Over the last decade, there has been increased attention in medical literature and media focused on mast-cell activation disorders. The mast cell is a ubiquitous cell in our bodies involved in many important roles in inflammation and immunity. What makes mast cells so interesting is that they have numerous receptors on their cell surface that, when activated, lead to the release of histamine and other bioactive mediators that can cause a host of clinical symptoms such as hives, swelling, itching, flushing, heart racing, dizziness, abdominal pain and diarrhea, among others. However, other medical conditions can present with the same symptoms that can be confusing to differentiate from mast cell disorders leading to misdiagnosis and incorrect or incomplete treatment.
Laypersons commonly associate the mast cell with allergic reactions like allergic rhinitis (hay fever), allergic asthma and food allergy, which occur when a genetically susceptible individual produces sensitizing allergic antibodies (immunoglobulin E or IgE) to a specific allergen like pollen, cat or a specific food like peanuts or tree nuts. When re-exposed to that allergen, IgE receptors on mast cells inhabited by these specific sensitizing IgE antibodies are activated to release histamine and other mediators that cause the symptoms described above. However, this allergic immune response only occurs in about 10–30% of the population who present with allergic symptoms. So, what about the other 70% of the population that present with allergy-like symptoms? We now know that mast cells have many other types of receptors that can be activated by non-specific triggers such as hot or cold temperatures, different medications or by neuropeptides released by nerve cells (neurons) that are in close communication with mast cells. This activation process can lead to very similar symptoms experienced by someone who doesn’t have allergies.
So, it is important when seeing your doctor for suspected mast cell activation syndrome (MCAS) to understand this condition is quite different from the run-of-the-mill allergic condition that the general public is familiar with. What makes this condition even more confusing is that experts in the field disagree on how to diagnose this condition. Some feel it is important to have evidence of an increased biomarker like serum tryptase, which is specifically made by mast cells, whereas others argue the condition could serve as a unifying diagnosis for multi-system disorders when no other explanation is found.
The currently accepted definition of MCAS requires three criteria for diagnosis: 1) symptoms consistent with a mast cell disorder like hives, swelling, itching, abdominal pain or diarrhea; 2) an elevated biomarker like a serum tryptase level released from activated mast cells and; 3) response to H1-antihistamines (fexofenadine, cetirizine, loratadine…). In my experience, most patients I see with concerns for MCAS do not meet these criteria and have multi-system involvement, which likely involves neurogenic pathways that are communicating with mast cells and other inflammatory cells and pathways in our body.
Thus, if you are experiencing a complex set of symptoms that are confusing to you and your physician that are impacting your daily lifestyle, don’t despair as personalized treatment by a physician experienced in mast cell disorders is often associated with a good clinical outcome. On a final note, this column is intended to discuss common medical conditions that Allergist/Immunologists may commonly see. Many of the concepts discussed are quite complex to understand completely, but, at the very least, it is hoped that these discussions will help to invoke thought and questions by the reader that can be further discussed with their physician or caregiver. Remember, an educated patient is a good patient!
