Article Outline
Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced or if their activation is out of proportion to the perceived threat to homeostasis. Mast cell activation syndrome refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release. Despite introduction of diagnostic criteria and some advances in treatment in the last decade, many areas of mast cell activation syndrome are in need of research. This article reviews our current knowledge about the various types of mast cell activation disorders, their treatment, and areas of uncertainty in need of future investigation.
Article
Disorders manifested by mast cell activation encompass a broad variety of diseases that can range from very rare to very common. Mast cell activation can be caused by both IgE-mediated and non–IgE-mediated triggers. On the common end of the spectrum, atopic disorders, such as allergic rhinitis and allergic asthma, can affect up to 10% to 30% of the general population.1 In contrast, mastocytosis and monoclonal mast cell activation syndrome (MMAS) might be as rare as 1 in 10,000 to 20,000 subjects.2 Disorders caused by mast cell activation might not necessarily have the mast cell as the central pathogenic component. Rather, mast cells might be reacting to stimuli generated by another pathologic process. By their nature, mast cells are designed to detect and respond to triggers of internal or external stress or danger.3 Therefore some level of mast cell activation might be physiologic or even necessary to maintain normal homeostasis on a day-to-day basis. The question then is when mast cell activation becomes a disorder.
There are 2 circumstances in which mast cell activation would result in pathologic clinical symptomatology. The first is when mast cells are produced abnormally, either qualitatively or quantitatively. This is the case in patients with clonal mast cell disorders in which the mast cell progenitor is affected by a neoplastic gain-of-function mutation, most commonly in KIT, a transmembrane receptor tyrosine kinase highly expressed by mast cells.4 The resulting neoplastic mast cells then accumulate in tissues and can interfere with tissue function or might release their mediators inappropriately, causing a variety of localized and systemic symptoms.
The second circumstance is when mast cell activation is out of proportion with the need to defend the body from the perceived danger. This might be the case when there is an imminent threat from infections, physical triggers, venoms, or allergens. An extreme example of inappropriate mast cell activation is anaphylaxis.
