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In the last two or three years, several Pathology Perspectives columns have focused on poorly understood, chronic, difficult-to-treat, and even more difficult- to-live-with conditions. We have looked at long COVID, fibromyalgia, postsepsis syndrome, dysautonomia, postural orthostatic tachycardia syndrome (POTS), chronic Lyme disease, and more—each one a somewhat controversial situation that can be hard to identify, especially since there are often differences of opinions about what they are, or even whether they exist. Mast cell activation syndrome (MCAS) fits into this category for several reasons. Although it has a strict set of diagnostic criteria, the majority of people who have the typical signs and symptoms of this condition do not meet that diagnostic standard—but that doesn't mean they aren't struggling. Also, MCAS occurs frequently with other long-term syndromes, and may be a contributing factor to them in ways that have yet to be discovered or confirmed. Or, it might be the other way around: Other disorders might set the stage for MCAS. It would be great to untangle this snarl of disorders and syndromes so that people who live with MCAS or any of its many partners might find some more useful management strategies. However, at this moment that's not a realistic expectation. In this article, we will explore MCAS and its relationship to other immune- system hypersensitivity syndromes (along with other conditions that at first glance have only a tenuous connection to MCAS) with an emphasis on where massage therapy might fit in this picture. Whether MCAS is common or not is a debatable question. But its signs and symptoms, which include extreme allergic reactions, fatigue, digestive discomfort, and more, are common. And while massage could be helpful for some clients with this condition, there are many ways our work might make it worse. That's why we need to understand as much as we can to make safe and effective clinical decisions. WHAT IS MCAS? Mast cell activation syndrome is among a group of disorders that affects mast cells: immune system cells distributed throughout the body that are involved with inf lammatory reactions. In MCAS, the number of mast cells stays constant but they become overreactive and secrete abnormally high levels of pro-inf lammatory chemicals. This distinguishes MCAS from mastocytosis, another mast cell disease, but mastocytosis involves the cloning of abnormal mast cells in various tissues, which can lead to extreme symptoms and, in some cases, a type of leukemia. 72 m a s s a g e & b o d y wo r k j a n u a r y/ fe b r u a r y 2 0 2 3 critical thinking | PATHOLOGY PERSPECTIVES Idiopathic Mast Cell Activation Syndrome A Tangle of Overlapping Conditions By Ruth Werner

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