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Mast Cell Activation Syndrome and Autoimmune Disease

Flushing, hives, stomach pain, diarrhea, fatigue, brain fog, and a racing heartbeat are all symptoms that can point in many directions. For some people, they appear during the search for an autoimmune diagnosis. However, in other cases, another condition known as mast cell activation syndrome (MCAS) may be involved.

In MCAS, mast cells, immune cells that normally help defend the body, become overly reactive.

They release histamine and other chemical messengers too often, or in response to harmless triggers like food, chemicals, or temperature changes.

This overreaction can look very similar to autoimmune disease, which is why MCAS often comes up while doctors are ruling out other causes.

The difference is important:

  • In autoimmune disease, the immune system mistakes the body’s own tissues for an enemy and attacks them, leading to lasting tissue damage.
  • In MCAS, the body isn’t attacking itself; it’s overreacting to things that shouldn’t be a threat.

Where they connect:

  • People with autoimmune disease may still have mast cell overactivity, which can intensify inflammation or make flares feel worse.
    • Research shows that mast cells themselves can take part in autoimmune pathways. For example, in chronic spontaneous urticaria (a condition marked by recurring hives), autoantibodies can activate mast cells and drive symptoms, illustrating the fine line between mast cell overactivity on its own (MCAS) and mast cell involvement in autoimmunity.
  • People with MCAS may also develop autoimmune conditions. This doesn’t mean one causes the other, but it shows how immune system problems can overlap.

Diagnosing MCAS is complex. 

Because mast cells are found throughout the body, in the skin, lungs, gut, and bone marrow, symptoms often affect multiple systems simultaneously. Doctors typically look for:

  • Symptoms in at least two organ systems (for example, skin and digestive tract)
  • Evidence of mast cell chemicals in blood or urine
  • Improvement with treatments that block or stabilize mast cells

MCAS is also part of a broader category called mast cell activation diseases (MCAD), which includes mastocytosis (where the body makes too many mast cells). Research shows MCAS can overlap with primary immunodeficiency, connective tissue disorders like Ehlers-Danlos, thyroid disease, and sometimes autoimmune disease, making the diagnostic process even more challenging.

Recognizing the differences between MCAS and autoimmune disease and how they occasionally overlap can help patients and doctors develop a clearer diagnosis and treatment plan.

Citations

Xu, Y., & Chen, G. (2015). Mast cell and autoimmune diseases. Mediators of inflammation, 2015, 246126. https://doi.org/10.1155/2015/246126

Koren, A., Dejanović, L., Rijavec, M., Kopač, P., Bizjak, M., Zidarn, M., Košnik, M., & Korošec, P. (2024). Autoimmune Mast Cell Activation Test as a Diagnostic Tool in Chronic Spontaneous Urticaria. International journal of molecular sciences, 25(17), 9281. https://doi.org/10.3390/ijms25179281