MCAS & POTS

In Dr. Hoffman’s words

What mast cell activation syndrome is

Mast cell activation syndrome (MCAS) is a group of disorders in which overactive mast cells episodically release a flood of inflammatory mediators, histamine among them, causing symptoms across many organ systems that wax and wane and often leave routine tests normal. Mast cells are white blood cells concentrated at the entrances to the body’s tissues: the eyes, nose, throat, skin, gut and lungs. When they activate they release over 200 signalling chemicals, including histamine, prostaglandins, leukotrienes and cytokines. In MCAS this protective function becomes upregulated and chronic, firing in response to things that are not a threat. Some experts estimate that 14 to 17 percent of the US population has MCAS, and it has been estimated to take up to 10 years to reach a diagnosis.

The history is usually the biggest clue. Allergies as a toddler, rashes that came and went, gut conditions that may have been misdiagnosed, anxiety, headaches, insomnia and poor wound healing. Flushing of the face and chest, feeling lightheaded on standing, ringing in the ears, overreaction to bee stings and mosquito bites, heat intolerance, and sensitivities to foods, chemicals and medications. Many people with MCAS have been told for years that their condition was psychosomatic.

How it is diagnosed

MCAS is not systemic mastocytosis. Mastocytosis is an increase in the number of mast cells and is most often diagnosed with the biomarker tryptase. MCAS is increased activity of a normal number of mast cells, so serum tryptase is rarely elevated, and throwing out the diagnosis because of a normal tryptase is a big mistake. I was a co-author of the peer-reviewed paper led by Dr. Lawrence Afrin, Diagnosis of mast cell activation syndrome: a global “consensus-2”, which sets out the revised, much broader criteria.

The five tests I consider most important are plasma histamine, 24-hour urine N-methylhistamine, plasma and 24-hour urine prostaglandin D2, and chromogranin A. Most must be chilled, because mast cell mediators are fleeting and degrade quickly if a specimen is not handled properly. Results fluctuate as symptoms wax and wane, and positive lab work is obtained only about 20 percent of the time, so tests often need repeating during a flare. NSAIDs and aspirin are stopped for five days before the prostaglandin tests, and proton pump inhibitors and H2 blockers for five days before chromogranin A, because they can falsely elevate it.

Histamine intolerance is a subset of MCAS

Histamine intolerance is considered present when there is more histamine in the body than it can cope with, usually because it is not broken down: a DAO enzyme deficiency in the gut, or an HNMT deficiency in the liver, with histamine in food adding to the load. In MCAS the mast cells secrete many mediators, not just histamine, so histamine release is only one piece of the puzzle. Histamine intolerance is a subset of MCAS, and anyone who has discovered they are histamine intolerant should also be tested for MCAS.

What triggers it

In my experience the top three triggers are early developmental trauma, mold and high-histamine, high-inflammatory foods, followed by metals, chemicals, infections, gut dysbiosis and EMFs. Other non-food triggers include temperature extremes, insect bites, chemicals in personal products, sodium benzoate, smoke, anesthetics, and medications that liberate histamine or block DAO. The highest-histamine foods are yeast and alcohol, fermented foods, cured and smoked meats and fish, shellfish, citrus, vinegar, berries such as strawberries, and leftover or aged food.

How it is treated

Treatment is layered and gradual. A low-histamine diet and gut support with probiotics and a DAO enzyme. Mast cell stabilizers, quercetin with vitamin C first among the natural ones. H1 and H2 blockers every 12 hours: antihistamines block the receptors rather than reducing histamine release, which is why round-the-clock blockade is needed, and it may take up to 12 months to reach maximum effect. Ketotifen at night as a sleep aid, mast cell stabilizer and H1 blocker. Then treating infections, removing toxins and allergens, supportive nutrients and herbs, a steady routine and less stress. When someone reacts to a medication, the culprit is often an excipient such as a dye, alcohol or povidone rather than the drug itself. Start with one or two changes and add a few each week.

POTS, and why I screen everyone for it

Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance in which the heart rate rises by at least 30 beats per minute in adults, or 40 in adolescents, within ten minutes of standing, without a drop in blood pressure, with symptoms lasting six months or more. Against a published figure of nine percent, I see MCAS in about half of my POTS patients, and hypermobile Ehlers-Danlos, POTS and MCAS have been described as a triad. I screen every patient with a 10-minute lying-standing test, pulse and blood pressure at one, three, five and ten minutes, because someone who does not perfuse the brain and mitochondria will not improve until it is treated.