MCAS: A Physician’s Perspective — Kelly McCann, MD, MPH
- By Trudie Mitschang
KELLY MCCANN, MD, MPH, is an integrative and functional medicine physician based in Costa Mesa, Calif. She earned her degrees in tropical medicine from Tulane University, and completed residencies in internal medicine and pediatrics. She is among a select group of physicians to complete the University of Arizona’s Residential Fellowship in Integrative Medicine under Andrew Weil, MD, and is certified by the Institute of Functional Medicine and board certified in integrative medicine.
BSTQ: What is mast cell activation syndrome (MCAS)?
Dr. McCann: MCAS is a condition in which mast cells, key immune “sentinel” cells, become dysregulated and overly reactive. Instead of responding appropriately to threats, they release chemical mediators like histamine, prostaglandins and cytokines too easily and too often, reactions that are often to things that do not really pose a threat such as smells or other common substances. This leads to widespread, multisystem symptoms that can appear inconsistent or unrelated. Unlike classic allergic reactions, MCAS is diffuse, unpredictable and frequently missed in conventional clinical settings.
BSTQ: How do patients with MCAS typically present?
Dr. McCann: Patients often arrive with a long list of symptoms affecting multiple organ systems. Common presentations include dermatologic symptoms like flushing, rashes and hives; gastrointestinal complaints such as abdominal pain, bloating and diarrhea; neurologic issues like headaches or dizziness; and cardiovascular symptoms, including palpitations or lightheadedness. Many also report anxiety or panic-like episodes. What’s striking is the pattern: Symptoms are episodic, encompass multiple systems of the body, triggered by seemingly unrelated exposures, and often occur despite normal standard lab work. Patients frequently describe a growing sensitivity to foods, environmental factors or even stress.
BSTQ: What do we know about the prevalence of MCAS?
Dr. McCann: Emerging data suggest MCAS may be far more common than previously thought, with some estimates indicating it could affect a significant portion of the population, up to 17 percent of the population or more. There also appears to be a genetic component, as individuals with a first-degree relative affected by MCAS have a higher likelihood of developing it.
BSTQ: How do you approach diagnosing MCAS in clinical practice?
Dr. McCann: Diagnosis is both clinical and laboratory-based. A thorough history is critical, looking for multisystem involvement, trigger patterns and symptom variability. Laboratory testing can include markers such as serum tryptase, histamine, prostaglandins and their metabolites, though these are not always elevated. Timing is important; testing during or shortly after a flare increases diagnostic yield. Equally important is assessing the patient’s environmental exposures, infectious history and nervous system regulation. MCAS rarely exists in isolation.
BSTQ: Once diagnosed, what does treatment typically involve?
Dr. McCann: Treatment is multifaceted and individualized. Broadly, we focus on three pillars: 1) trigger identification and removal, which may involve environmental testing for mold, addressing chronic infections and reducing toxic exposures; 2) mast cell stabilization, using both pharmacologic and non-pharmacologic approaches; and 3) nervous system regulation techniques that support autonomic balance, such as breathwork, vagal nerve stimulation and trauma-informed therapies. The goal is not just symptom suppression but restoring stability to the system.
BSTQ: There’s growing discussion about reframing MCAS. Can you explain that perspective?
Dr. McCann: MCAS has been viewed as a condition of dysfunction requiring suppression management. An emerging perspective is that mast cell activation is an exaggerated but meaningful response to perceived threat. Symptoms, then, are signals rather than random malfunctions pointing to underlying environmental, infectious or physiologic stressors that need to be addressed. For clinicians, this framework encourages a more comprehensive, root-cause approach rather than focusing solely on symptom control. And beneath the physical symptoms and stressors are even deeper patterns of beliefs, trauma and lack of safety that drive the threat response.