Mast cell activation and histamine intolerance
MCAS, mast cell activation syndrome
Chronic conditionMast cells are immune cells that release histamine and other chemicals. In mast cell activation syndrome, they release them too easily, causing flushing, hives, gut symptoms, and sometimes anaphylaxis.
Medical Disclaimer
For education only — this guide can't diagnose you. If these signs sound familiar, talk with a healthcare provider. Book a consult
What happens
Mast cells sit in the skin, gut, and airways and drive allergic reactions. MCAS is diagnosed only when three things are present: episodes affecting two or more body systems at once, a rise in blood tryptase during an episode compared with your baseline level, and improvement with medicines that block mast cell chemicals. Many people have similar symptoms without meeting these criteria, and the label is sometimes used too loosely. Some people have a high baseline tryptase from an inherited trait (hereditary alpha-tryptasemia) or, rarely, mastocytosis. 'Histamine intolerance' describes symptoms after high-histamine foods, thought to come from low levels of the enzyme DAO. The evidence for it is limited, and DAO blood tests haven't been shown to diagnose it reliably.
Who gets it
Most people evaluated for MCAS or histamine intolerance are women. Many also have POTS or hypermobile Ehlers-Danlos syndrome, though how these are linked isn't clear. Hereditary alpha-tryptasemia, found in about 5 percent of people, is linked to more allergic-type symptoms. Allergies, asthma, and chronic hives can cause similar symptoms and are much more common.
Signs worth getting checked
- Flushing or a sudden feeling of warmth
- Hives, itching, or swelling
- Belly cramps, diarrhea, or nausea
- Nasal congestion or wheezing
- Lightheadedness, a racing heart, or low blood pressure
- Headaches or brain fog
- Reactions triggered by heat, alcohol, NSAIDs, stress, or certain foods
Labs to ask about
- Baseline blood tryptase
- Tryptase drawn within 4 hours of an episode, compared with your baseline
- Urine tests for histamine and prostaglandin breakdown products, collected during or right after an episode
- Allergy testing to look for specific triggers
- Genetic testing for hereditary alpha-tryptasemia, or tests for mastocytosis, if baseline tryptase is high
Treatments your doctor may discuss
- Non-drowsy H1 antihistamines, sometimes at higher doses
- H2 blockers such as famotidine
- Cromolyn, a mast cell stabilizer, for gut symptoms
- Montelukast, or omalizumab for severe cases
- An epinephrine auto-injector if you've had anaphylaxis
Supportive steps to discuss with your provider
- Keep a symptom and trigger diary, and note what you ate, did, and took before each episode.
- Ask whether a short low-histamine diet trial makes sense, with a plan to add foods back. Avoid long-term restrictive diets.
- Be cautious about paying for DAO blood tests or DAO supplements. The evidence for both is limited.
- Carry your epinephrine auto-injector if it's prescribed, and show people close to you how to use it.
- Before surgery, procedures, or contrast dye, tell the team you have a mast cell condition.
See a doctor promptly if you have
- Trouble breathing, throat or tongue swelling, or fainting: use epinephrine if you have it and call 911
- Hives or flushing with vomiting, dizziness, or a racing heart: call 911
- Episodes that are becoming more frequent or severe
- Bone pain, an enlarged spleen, or lasting reddish-brown skin spots
- Ongoing diarrhea or unintended weight loss
Related conditions
Ready to find the root cause?
Dr. Lesher is a Naturopathic Doctor who focuses on autoimmune and chronic conditions in women. Since 2020, she's helped hundreds of patients stop managing symptoms and start healing.