Mast-Cell Activation Syndrome

Should a patient with mast cell activation syndrome be treated the same way as a patient experiencing an allergic reaction or anaphylaxis?I recently attended a patient with known mast cell activation syndrome following a motor vehicle collision with a deer. While we were responding, we were advised that the patient had already used two epinephrine auto-injectors.On arrival, the patient was in respiratory distress and reported feeling unable to breathe. She could speak only briefly because talking appeared to worsen throat irritation and the sensation that her airway was closing. Her lung sounds were clear but diminished because she was unable to take a deep breath. Her oxygen saturation was 98%, and she was tachycardic and hypertensive.The patient’s family stated that stress can trigger her mast cell activation syndrome and that she usually requires additional epinephrine. Following consultation with a base hospital physician, diphenhydramine was authorized, with further epinephrine to be given if the patient’s condition deteriorated.In a similar situation, should the patient be treated directly under the anaphylaxis directive, or is a patch required because the episode was triggered by stress rather than exposure to a known or suspected allergen?

Acute mast cell activation syndrome episodes with airway compromise, bronchospasm, hypotension, or multisystem involvement are managed using the same clinical approach as systemic anaphylaxis. Intramuscular epinephrine remains first-line treatment, with bronchodilators and antihistamines used as adjuncts. Corticosteroids may be considered but do not provide immediate benefit during the acute episode (Weiler et al., 2019; Castells & Butterfield, 2019).

In this case, the treatment provided was clinically appropriate. The patient had ongoing respiratory symptoms despite two self-administered doses of epinephrine, making further epinephrine, bronchodilator therapy, and supportive management reasonable. The lack of urticaria, hypoxemia, or hypotension does not exclude anaphylaxis or clinically significant mast cell activation, particularly when upper-airway or respiratory symptoms are present.

However, treatment appropriateness and directive authorization are separate questions. The current anaphylaxis directive is written around exposure or suspected exposure to an allergen. A stress-triggered MCAS episode does not clearly meet that prerequisite, even though the underlying mediator release and acute treatment are similar. Therefore, the episode would not technically fall within the spirit or wording of the existing directive, and a patch would be required before administering medications under that directive. Patching was particularly appropriate because the presentation was atypical and symptoms persisted after two epinephrine doses.

References

Castells, M., & Butterfield, J. (2019). Mast cell activation syndrome and mastocytosis: Initial treatment options and long-term management. The Journal of Allergy and Clinical Immunology: In Practice, 7(4), 1097–1106.

National Comprehensive Cancer Network. (2026). NCCN clinical practice guidelines in oncology: Systemic mastocytosis(Version 3.2026).

Theoharides, T. C., Valent, P., & Akin, C. (2015). Mast cells, mastocytosis, and related disorders. The New England Journal of Medicine, 373(2), 163–172.

Weiler, C. R., Austen, K. F., Akin, C., Barkoff, M. S., Bernstein, J. A., Bonadonna, P., Butterfield, J. H., Carter, M., Fox, C. C., Maitland, A., Pongdee, T., Mustafa, S. S., Ravi, A., Tobin, M. C., Vliagoftis, H., Schwartz, L. B., & AAAAI Mast Cell Disorders Committee. (2019). AAAAI Mast Cell Disorders Committee work group report: Mast cell activation syndrome diagnosis and management. The Journal of Allergy and Clinical Immunology, 144(4), 883–896.